We evaluated the involvement of nitric oxide (NO) in the early hemodynamic response to uninephrectomy (UNX) in rats. Animals were uninephrectomized, and 48 h after removal of the kidney, the effect of infusing N-G-nitro-L-arginine methyl ester (L-NAME) on renal function was studied. Glomeruli were isolated, and glomerular nitrite and cGMP productions were measured. In addition, endothelial constitutive NO synthase (NOS III) and inducible NO synthase (iNOS) were assessed by Western blot and by measuring the conversion of arginine to citrulline. UNX animals showed an increase in renal plasma flow that was inhibited by L-NAME in a higher proportion than in sham-operated (SO) animals. No differences were observed in systemic NO-dependent vascular tone, since mean arterial pressure showed similar increments in SO and UNX rats. Glomeruli from UNX animals showed an increase in glomerular nitrite production that was blunted by L-NAME addition.Also, cGMP levels were increased in glomeruli from UNX animals,and this increase was inhibited by L-NAME. Western blot analysisshowed no differences in NOS III but a higher iNOS amount in glomerulifrom UNX than in those from SO rats. No significant differencesbetween UNX and SO rats were found in calcium-dependent NOS enzymatic activity in the renal cortex. However, calcium-independent enzymaticactivity was markedly higher in the renal cortex of UNX than inthose from SO animals. In conclusion, glomeruli from rats 48 h after UNX had a greater production of NO than those from SO animals.This increased glomerular NO production is based on an increasein the iNOS isoform. Increased glomerular NO synthesis seems to play a role in the decreased renal vascular resistance observedafter unilateral nephrectomy in rats.
Renal metabolism of uric acid in type I insulin-dependent
diabetic patients: relation to metabolic compensation.
González-Sicilia
L, García-Estan
J, Martínez-Blázquez
A, Fernández-Pardo
J, Quiles
JL, Hernández
J
Horm Metab Res 1997 Oct 29:10 520-3
Patients with insulin-dependent diabetes mellitus and poor glycemic control show hypouricemia with hyperuricosuria. In the present study, we have evaluated whether a good glycemic control influences the renal handling of uric acid. Sixteen patients (8 male, mean age 22.4 +/- 7.2 years) were studied under two situations, poor glycemic control (glycemia > 11 mmol/L and HbA1 c > 10%) and good glycemic control (glycemia < 6 mmol/L and HbA1 c < 8.5%). A group of 16 normal subjects served as the control group (8 male, mean age 21.9 +/- 9.1 years). In the poor glycemic control phase, patients showed lower plasma uric acid levels (0.18 +/- 0.06 mmol/L) and higher fractional urinary excretion of uric acid (16.1 +/- 9.3%) than the controls (0.28 +/- 0.06 and 8.2 +/- 1.9%, respectively). When a good glycemic control was reached, plasma uric acid increased (0.22 +/- 0.05), but it was still lower than that of the controls and fractional excretion of UA was normalized. Plasma uric acid was inversely correlated to glycemia (r = -0.34, p < 0.05) and to HbA1 c (r = -0.56, p < 0.0008) and fractional excretion of uric acid was directly correlated to glycemia (r = 0.39, p < 0.03) and HbA1 c (r = 0.73, p < 0.00005). These results indicate that the hypouricemia and hyperuricosuria of insulin-dependent diabetes mellitus is corrected by an adequate glycemic control, suggesting that these alterations are of a functional origin and due to a defective metabolic control.
Age-related changes in the pressure diuresis and natriuresis
response.
Vargas
F, Ortíz
MC, Fortepiani
LA, Atucha
NM, García-Estan
J
Am J Physiol 1997 Aug 273:2 Pt 2 R578-82
The renal-excretory responses to changes in renal perfusion pressure (RPP) were studied in anesthetized young (3 mo old), adult (12 mo old), and senescent (24 mo old) rats to evaluate whether the pressure diuresis and natriuresis mechanism is altered as a function of age. Experiments were performed in anesthetized animals in which nervous and systemic hormonal influences to the kidney were fixed. Mean arterial pressure was similar in all three groups: 97.6 +/- 2.6, 102.1 +/- 3.7, and 95.2 +/- 5.2 mmHg in young, adult, and senescent rats, respectively. The relationships between RPP and diuresis/natriuresis or fractional excretions of water and sodium were similar in young and adult rats. However, in senescent rats the pressure-diuretic and pressure-natriuretic responses were slightly shifted to the right, so that diuresis and natriuresis were significantly lower at higher levels of RPP. Glomerular filtration rate was well autoregulated, and there were no differences between young and adult rats at each level of RPP. However, a significantly lower glomerular filtration rate was observed in senescent rats. These results indicate an age-related decline in the pressure-dependent sodium and water excretion that appears to be due to a decrease in glomerular filtration and an increase in tubular sodium reabsorption.
Importance of nitric oxide and prostaglandins in the
control of rat renal papillary blood flow.
Ortiz
MC, Atucha
NM, Lahera
V, Vargas
F, Quesada
T, Garcia-Estan
J
Hypertension 1996 Mar 27:3 Pt 1 377-81. Full text
The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has been studied in anesthetized Munich-Wistar rats by use of laser Doppler flowmeter. Acute administration of Nw-nitro- L -arginine methyl ester (L-NAME) 10 mg/kg IV (n=8) increased mean arterial pressure by 27.8±3.6%, decreased papillary blood flow by 39.4±3.8%, and decreased renal blood flow by 47.4±1.9%. The subsequent administration of indomethacin (7.5 mg/kg IV) further decreased papillary blood flow (35.2±2.5%) without significant changes in mean arterial pressure or renal blood flow. In a second group (n=6), administration of indomethacin before L-NAME decreased papillary blood flow by 39.6±2.1% without significantly altering mean arterial pressure or renal blood flow. The subsequent injection of L-NAME further decreased papillary blood flow (32.9±1.8%) and renal blood flow (49.8±6.6%) while increasing mean arterial pressure to a level not significantly different from that found in the first group. Autoregulation studies showed that L-NAME but not indomethacin reduced the renal perfusion pressure–renal blood flow relationship without altering autoregulation. However, both nitric oxide and prostaglandins importantly affected the renal perfusion pressure–papillary blood flow relationship because L-NAME and indomethacin significantly decreased this relationship in an additive fashion. Although both drugs reduced the sensitivity of the pressure–papillary flow relationship, only L-NAME affected autoregulation so that papillary blood flow was autoregulated at higher renal perfusion pressures. Thus, the present results indicate that both nitric oxide and prostaglandins control a similar percentage of rat renal papillary blood flow, but nitric oxide seems to be more important than prostaglandins as a mediator of the pressure–blood flow relationship. In contrast, only nitric oxide modifies the renal blood flow level, although it does not disturb whole-kidney blood flow autoregulation.
Endothelium-dependent and endothelium-independent vasodilation
in hyperthyroid and hypothyroid rats.
Vargas
F, Fernández-Rivas
A, García-Estañ J, García
del Rio C
Pharmacology 1995 Nov 51:5 308-14
The effects of hyper- and hypothyroidism on the vasorelaxing responses to acetylcholine (ACh), sodium nitroprusside (NP), and CaCl2 were investigated in aortic strips and isolated perfused kidneys. The renal vascular reactivity to ACh and NP was increased in hyperthyroid rats, whereas the concentration-response curve to ACh in hypothyroid rats was flattened. In the renal vasculature from hypothyroid rats, NP produced a dual response: vasoconstriction at low doses and vasodilation at medium to high doses. Aortic strips from hyperthyroid rats showed an increased response to ACh without significant differences between hypothyroid and control groups. Aortic strips from all three experimental groups showed a similar relaxing response to CaCl2. These results indicate that: (1) the raised arterial pressure of hyperthyroid rats is not associated with a reduced endothelium-dependent and calcium-induced vasodilation, and (2) the changes in responsiveness to vasodilators in resistance vessels from hyper- and hypothyroid rats may play a role in the increased and decreased peripheral vascular resistances, respectively, previously reported in such animals.
Pressure-diuresis-natriuresis response in hyperthyroid
and hypothyroid rats.
Vargas
F, Atucha
NM, Sabio
JM, Quesada
T, García-Estan
J
Clin Sci (Colch) 1994 Sep 87:3 323-8
1. Renal responses to changes in renal perfusion pressure were studied in anaesthetized hyperthyroid (thyroxine, 300 micrograms day-1 kg-1) and hypothyroid (methimazole, 0.03% via drinking water) rats to determine whether an abnormality in the pressure-diuresis-natriuresis phenomenon is involved in the resetting of kidney function in these disorders. 2. There were no significant differences between control and hypothyroid rats with respect to the relationships between renal perfusion pressure and absolute or fractional water and sodium excretion. However, in hyperthyroid rats the pressure-diuresis-natriuresis mechanism was impaired. 3. Renal blood flow and glomerular filtration rate were well autoregulated and there were no differences between control and hypothyroid rats at every level of renal perfusion pressure. A significantly lower glomerular filtration rate was observed in hyperthyroid rats when data were expressed per gram kidney weight, but glomerular filtration rate was similar to that of control rats when normalized by body weight. 4. The shift in the pressure-diuresis-natriuresis response of hyperthyroid rats is mainly due to an increase in tubular reabsorption. Blunting of the renal pressure-diuresis-natriuresis mechanism in hyperthyroid rats may represent the functional resetting of the kidney necessary for sustained hypertension. However, a normal pressure-natriuresis response was observed in hypothyroid rats, in which blood pressure was markedly reduced.
Effects of Nw-nitro L-arginine methyl ester on the
response to NaCl load in hyper- and hypothyroid rats.
Sabio
JM, García-Estan
J, García
del Río C, Vargas
F
Horm Metab Res 1994 Sep 26:9 409-12
We assessed the effects of the inhibition of endogenous nitric oxide (NO) synthesis with Nw-nitro-L-arginine methyl ester (L-NAME) on water and sodium handling after NaCl load containing the inhibitor at 0, 0.5, 5 and 50 mg/kg in conscious control, hyper- and hypothyroid rats. L-NAME at 0.5 mg/kg caused a similar decrease in diuresis and natriuresis in control and hypothyroid rats, whereas no changes were seen in the hyperthyroid group. The saline load with 5 mg/kg of L-NAME produced no significant changes with respect to the 0 dose in any variable in control and hypothyroid rats, but increased natriuresis in the hyperthyroid group. The highest dose of L-NAME (50 mg/kg) increased the diuretic and natriuretic response in control and hyperthyroid groups, whereas in the hypothyroid group no urinary variable was significantly modified with respect to the 0 dose. These results indicate that the antidiuretic and antinatriuretic effects of L-NAME at low doses are suppressed in hyperthyroid rats, whereas the diuretic and natriuretic effects at high doses are absent in hypothyroid rats. Our findings suggest that the modulatory role of NO on sodium and water excretion is affected in both thyroid disorders. In addition, the highest dose of L-NAME killed hyperthyroid rats, indicating that NO plays an essential role for life in hyperthyroidism.
Role of nitric oxide in the systemic circulation of
conscious hyper- and hypothyroid rats.
Vargas
F, Montes
R, Sabio
JM, García-Estan
J
Gen Pharmacol 1994 Sep 25:5 887-91
1. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO biosynthesis, which blocks basal NO production, caused a similar increase of mean arterial pressure (MAP) in control hyper- and hypothyroid rats at the lowest dose, however, smaller pressor effects were observed with increasing doses in hyper- and hypothyroid rats. An additional dose of L-NAME (30 mg/kg), which produced no further increase in pressure, killed 90% of the hyperthyroid rats, whereas hypothyroid and control rats survived this additional dose. 2. The systemic responses to acetylcholine (ACh), an endothelium-dependent vasodilator that stimulates NO production/release, were significantly increased in hypothyroid rats, while hyperthyroid rats showed no significant differences when compared with controls. However, 10(-8) M ACh killed hyperthyroid rats, whereas control and hypothyroid rats survived this dose. 3. The maximal hypotensive response to sodium nitroprusside (SNP), an agonist that generates NO, was similar in intact controls, hyper- and hypothyroid rats. 4. These data indicate that hyper- and hypothyroidism show a reduction in basal NO synthesis/release, this reduced systemic NO tone being essential for life in hyperthyroid rats; whereas the response to ACh is not reduced and the hypotensive response to SNP did not differ between groups, indicating that the responsiveness of the systemic circulation to NO is not altered in either thyroid disorder.
Effects of nitric oxide inhibition on the renal papillary
blood flow response to saline-induced volume expansion in the rat.
Atucha
NM, Ramírez
A, Quesada
T, García-Estan
J
Clin Sci (Colch) 1994 Apr 86:4 405-8
1. Evidence indicates that nitric oxide (NO) exerts a paracrine influence in the renal medulla. Increases in papillary blood flow are thought to be an important determinant of the renal response to extracellular volume expansion. Therefore, in the present study, we have evaluated the role of NO in mediating papillary blood flow (laser-Doppler flowmetry) and excretory responses to volume expansion with isotonic saline (3% body weight, 15 min). 2. Infusion of the NO synthesis inhibitor N omega-nitro-L-arginine methyl ester (10 micrograms min-1 kg-1), significantly attenuated the renal diuretic and natriuretic responses to volume expansion as well as the renal hydrostatic interstitial pressure increase induced by this manoeuvre. The percentages of the water and sodium excreted in 1 h by the N omega-nitro-L-arginine methyl ester-pretreated animals were 36% and 40% of the load, whereas those of the control animals were 44% and 65%, respectively. 3. In similar experiments performed in the exposed papilla of Munich Wistar rats, the same dose of N omega-nitro-L-arginine methyl ester reduced basal papillary blood flow and blunted the elevation in papillary blood flow induced by volume expansion (6% versus 16% in the control animals). 4. These results indicate that the inhibition of NO synthesis blunts the renal excretory and papillary responses to volume expansion, suggesting that NO modulates these responses through changes in papillary blood flow and renal interstitial hydrostatic pressure.
Role of renal interstitial hydrostatic pressure in
natriuretic response to ANP.
García-Estan
J, Roman
RJ
Am J Physiol 1990 Jun 258:6 Pt 2 R1333-9
The present study evaluated the role of changes in renal interstitial hydrostatic pressure (RIHP) in the natriuretic response to atriopeptin III (AP III). In control animals, infusion of AP III (100 ng.kg-1.min-1 iv) increased fractional excretion of sodium, potassium, lithium, and water while glomerular filtration rate and renal blood flow were unaltered. The natriuretic response to AP III was associated with a significant elevation in RIHP from 5.6 +/- 0.8 to 8.1 +/- 1.0 mmHg. In rats pretreated with amiloride (1 mg/kg) to block sodium transport in the collecting duct, basal sodium excretion was elevated, but infusion of AP III still increased RIHP and the fractional excretion of sodium, water, and lithium by the same amount as was observed in the control animals. Removal of the renal capsule completely blocked the rise in interstitial pressure in the renal cortex in amiloride-treated rats, but it did not eliminate the elevation in sodium, water, and lithium excretion produced by AP III. To determine whether changes in renal medullary interstitial pressure could play a role in the residual natriuretic response to AP III in these animals, cortical and medullary interstitial pressure were simultaneously measured in rats with a decapsulated kidney. In this group, AP III increased renal medullary interstitial pressure, while cortical interstitial pressure was unaltered. These results are consistent with the view that changes in renal medullary hemodynamics and RIHP contribute to the natriuretic effect of atrial natriuretic peptide by elevating distal delivery of sodium from deep nephrons.
Pressure-diuresis in volume-expanded rats. Cortical
and medullary hemodynamics.
Roman
RJ, Cowley
AW Jr, Garcia-Estan
J, Lombard
JH
Hypertension 1988 Aug 12:2 168-76
This study evaluated whether pressure-diuretic and pressure-natriuretic responses are associated with alterations in vasa recta hemodynamics. Autoregulation of cortical and papillary blood flow was studied using a laser-Doppler flowmeter in volume-expanded and hydropenic rats. Superficial cortical flow and whole kidney renal blood flow were autoregulated in volume-expanded rats and decreased by less than 10% after renal perfusion pressure was lowered from 150 to 100 mm Hg. In contrast, papillary blood flow was not autoregulated and fell by 24 +/- 2%. The failure of papillary blood flow to autoregulate was due to changes in the number of perfused vessels as well as to alterations in blood flow in individual ascending and descending vasa recta. Pressure in vasa recta capillaries increased from 6.8 +/- 0.8 to 13.8 +/- 1.2 mm Hg after renal perfusion pressure was elevated from 100 to 150 mm Hg, and renal interstitial pressure rose from 7.4 +/- 0.8 to 12.3 +/- 1.4 mm Hg. In hydropenic rats, papillary blood flow was autoregulated to a significant extent, but it still decreased by 19% after renal perfusion pressure was lowered from 150 to 100 mm Hg. The pressure-diuretic and pressure-natriuretic responses in hydropenic rats were blunted in comparison to those observed in volume-expanded rats. These findings indicate that the pressure-diuretic and pressure-natriuretic responses are associated with changes in vasa recta hemodynamics and renal interstitial pressure.
Effect of captopril on norepinephrine vascular contractility.
Ubeda
M, Fenoy
F, Carbonell
LF, Salazar
F, García-Estan
J, Salom
M, Quesada
T
Gen Pharmacol 1985 16:3 303-6
In isolated aortic rings and in vitro perfused mesenteric arteries of Wistar rats the vasoconstrictor responses to norepinephrine (NE) were not affected by captopril (2 X 10(-4) M). However, captopril (1 mg/kg i.v.) in pithed Wistar rats attenuated significantly the increases in diastolic blood pressure induced by NE. In pithed rats the effect of captopril on NE diastolic blood pressure responses disappeared either in the presence of an angiotensin II (5 ng X kg-1 X min) infusion or when the rats were previously nephrectomized. These findings suggest that the effect of captopril on vascular responses to norepinephrine is mediated by an inhibition of the renin-angiotensin system and not by an antagonistic effect on alpha-adrenergic receptors.
Normal hemodynamic parameters in conscious Wistar rats.
Carbonell
LF, Salom
MG, Salazar
FJ, García-Estan
J, Ubeda
M, Quesada
T
Rev Esp Fisiol 1985 Dec 41:4 437-42
The evolution of different hemodynamic parameters with ponderal growth has been studied in conscious Wistar rats. The thermodilution method has been used to determine cardiac output and related variables. The results suggest that, between animal weight and the different hemodynamic parameters, there is a direct proportional relationship to blood volume, mean arterial pressure, cardiac output, stroke volume and total peripheral resistance, and an indirect proportional relationship to heart rate, cardiac index and stroke volume index. Body weight, therefore, plays a major role in hemodynamic determination, this having to be kept in mind when designing the experiment.
Sympathoadrenal activity and plasma glucose effects
on plasma dopamine-beta-hydroxylase levels in rats.
Muñoz
JA, Garcia-Estan
J, Salom
MG, Quesada
T, Miras
Portugal MT
Clin Chim Acta 1985 Nov 15 152:3 243-52
Plasma dopamine-beta-hydroxylase (DBH) activity is a controversial index of sympathoadrenal function. In our results, the half-life of bovine DBH administered by cardiac puncture to Wistar rats was dependent on plasma glucose values, being 60 min for controls, 96 min for streptozotocin (STZ)-diabetic animals (p less than 0.02) and 33 min for insulin-treated normal rats (p less than 0.01). In experimental situations with low plasma glucose levels, DBH activity was also diminished with respect to controls (glucose: 103.6 +/- 2.2 mg%, DBH: 9.7 +/- 0.5 U/ml). After fasting, glucose was 60.8 +/- 1.5 mg% (p less than 0.001) and plasma DBH 6.4 +/- 0.3 U/ml (p less than 0.001); fasting plus cold exposure also decreased glucose (66.2 +/- 1.4 mg%, p less than 0.001) and plasma DBH (6.7 +/- 0.2 U/ml; p less than 0.001). In both situations, there was an increase in exocytosis from sympathoadrenal tissues; however, no increase in plasma DBH levels was observed, because plasma glucose being diminished it was unable to compete at the catabolic receptor level. When normal plasma glucose levels take place, plasma DBH is essentially constant, poorly reflecting a moderate increase or decrease in exocytosis from tissues, as was the case in our animals with 48 h of cold exposure. When chemical sympathectomy (6-OH-dopamine) or bilateral adrenalectomy was performed there was a compensatory mechanism between them. Plasma DBH does not change significantly in these situations if plasma glucose values are normal. From these results, the most important physiological influence on plasma DBH activity is the glucose plasma levels. Plasma DBH values not being a useful index of sympathoadrenal activity if, at the same time, the plasma glucose levels are not considered.
Dopamine-beta-hydroxylase activity in adrenal gland
and spleen of rats after fasting and cold exposure.
García-Estan
J, Munoz
JA, Serrano
MC, Carbonell
LF, Miras
Portugal MT, Quesada
T
Experientia 1985 Jan 15 41:1 61-2
Fasting (48 h) results in dopamine-beta-hydroxylase (DBH) release both in adrenal gland and spleen, suggestive of an increase in the activity of these organs. Cold exposure (48 h) produces a dissociation of the sympathoadrenal response. When both stimuli are simultaneously employed, the DBH response suggests the preponderance of the response to fasting. Plasma DBH is decreased in all groups studied, this could be due to its half-life and the splenic DBH depletion.
Blood pressure control in pithed rat.
Carbonell
LF, García-Estan
J, Ubeda
M, Salom
MG, Fenoy
F,
Quesada T
Gen Pharmacol 1986 17:4 469-72
In the pithed Wistar rats Captopril (2 mg/kg) decreased the mean arterial pressure (MAP) 21%. Further injection of a specific antagonist decreased the vasoconstrictor action of vasopressin (aAVP, 10 micrograms/kg) an additional 6%. Reversal in the order of drug administration did not change these percentages. The osmotic stimulus evoked by the infusion of hypertonic saline (ClNa 9%, 0.018 ml/min, 2 hr) significantly increased MAP, this increase being almost totally reversed by the aAVP (10 micrograms/kg). These findings suggest a greater role of the renin-angiotensin system than of the vasopressin (AVP) in the maintenance of MAP in the pithed rat; AVP, moreover, can be released by means of an osmotic stimulus.
Dopamine-beta-hydroxylase activity in plasma, spleen
and adrenal gland of streptozotocin-diabetic rats: correlation with cataracts.
Munoz
JA, García-Estan
J, Canteras
M, Quesada
T, Miras-Portugal
MT
Rev Esp Fisiol 1986 Mar 42:1 63-70
In streptozotocin-diabetic rats a large increase in plasma dopamine-beta-hydroxylase activity was observed. This increase returned to control values with sufficient insulin doses (6 I.U/day); lower insulin doses did not allow normal level to be reached, a dose-dependent decrease being observed. Although the glycemia levels in the diabetic state are responsible for the plasma dopamine-beta-hydroxylase, there is no exact ratio between these two parameters when diabetic animals are treated with different insulin doses which suggests not only the clearance of plasmatic dopamine-beta-hydroxylase, but a contribution from exocytotic tissues as well. In the experimental conditions, before cataracts appeared, the animals about to develop opaque lenses showed a greater dopamine-beta-hydroxylase activity than those which were to remain without this complication. After three months in diabetic state, the severity of disease was evident in the animals with cataracts since they showed a significantly higher function of the sympathoadrenal axis, expressed in spleen and adrenal dopamine-beta-hydroxylase activity. Plasma dopamine-beta-hydroxylase, as a minority glycoprotein can be considered a useful parameter of other mannose-terminal glycoproteins without having a well-known function, and also as a high risk protein, the accumulation of which in several places contributes to the complex pathogenic mechanism of diabetes complications.
Hemodynamic alterations in chronically conscious unrestrained
diabetic rats.
Carbonell
LF, Salom
MG, Garcia-Estan
J, Salazar
FJ, Ubeda
M, Quesada
T
Am J Physiol 1987 May 252:5 Pt 2 H900-5
Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dtmax and dP/dtmin of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic state, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.
Hemodynamic effects of hypertonic saline in the conscious
rat.
Garcia-Estan
J, Carbonell
LF, Garcia-Salom
M, Salazar
FJ, Quesada
T
Life Sci 1989 44:19 1343-50
The present study examines the role of vasopressin and the sympathetic nervous system on the hemodynamic effects of an infusion of hypertonic saline (NaCl 1.5 M) in conscious rats. The cardiovascular response to hypertonic saline was similar in both untreated and hexamethonium-pretreated rats. Mean arterial pressure increased by 15 mmHg as a consequence of the elevation of total peripheral resistance, while cardiac index was decreased. The administration of an antagonist to the pressor activity of vasopressin in rats with intact reflexes, partially decreased mean arterial pressure and total peripheral resistance and increased cardiac index toward basal values. In contrast, the hemodynamic response to hypertonic saline was totally reverted when the vasopressin antagonist was injected in the hexamethonium-pretreated rats. The results of the present study indicate that the hypertensive response induced by hypertonic saline in conscious rats is due to the vasoconstrictor effects of both vasopressin and the sympathetic nervous system.
Natriuretic effect of atriopeptin III in rats with
papillary necrosis.
Garcia-Estan
J, Takezawa
K, Roman
RJ
Am J Physiol 1989 Nov 257:5 Pt 2 F859-65
This study compared the effects of atriopeptin III (AP III) on sodium excretion and renal interstitial hydrostatic pressure (RIHP) in control rats and in rats pretreated with 2-bromoethylamine (BEA) to produce papillary necrosis. In control rats, infusion of AP III (100 ng.kg-1.min-1) increased sodium excretion from 2.2 +/- 0.7 to 6.4 +/- 0.9 microeq.min-1.g kidney wt-1 and RIHP from 6.8 +/- 0.7 to 8.7 +/- 0.9 mmHg, whereas glomerular filtration rate and renal blood flow were unaltered. Similar results were obtained in rats pretreated with BEA 48 h before the experiment. In rats studied 6 wk after BEA treatment, the papilla was absent and there was atrophy of juxtamedullary nephrons. AP III did not alter sodium excretion or RIHP in this group of rats. These results indicate that 1) an intact renal papilla and/or juxtamedullary nephron population may be required for the natriuretic effect of AP III; 2) the papillary injury 48 h after BEA is not sufficient to abolish the natriuretic response to AP III; and 3) elevations in RIHP may play a role in the natriuretic response to AP III.
Effects of complement depletion on glomerular eicosanoid
production and renal hemodynamics in rat nephrotoxic serum nephritis.
Garcia-Estan
J, Roman
RJ, Lianos
EA, Garancis
J
J Lab Clin Med 1989 Oct 114:4 389-93
The role of complement in mediating the changes in renal hemodynamics and glomerular eicosanoid synthesis after the administration of heterologous antibody against rat glomerular basement membrane (AGBM) was studied in Munich-Wistar rats. AGBM serum decreased glomerular filtration rate (GFR) and increased glomerular thomboxane B2 (TxB2) production without associated changes in glomerular prostaglandin E2 (PGE2) or PGF2 alpha production. Pretreatment of rats with cobra venom factor to deplete complement blocked the fall in GFR produced by AGBM without altering the increment in glomerular TxB2 production. In these animals, glomerular PGE2 synthesis was elevated. The results indicate that the salutary effects of complement depletion in nephrotoxic serum nephritis are not mediated by changes in the glomerular production of the vasoconstrictor TxA2. An enhanced production of PGE2 may participate in preventing the fall in GFR after AGBM administration in the complement-depleted rats.
Role of renal interstitial hydrostatic pressure in
the pressure diuresis response.
Garcia-Estan
J, Roman
RJ
Am J Physiol 1989 Jan 256:1 Pt 2 F63-70
The present study examines the role of renal interstitial hydrostatic pressure (RIHP) in the pressure-diuretic and -natriuretic response. The relationships between RIHP, sodium excretion, and renal perfusion pressure (RPP) were determined in antidiuretic and volume-expanded (VE) rats with an intact or decapsulated kidney. RIHP was measured by use of the implanted capsule technique. RIHP increased significantly from 7.5 +/- 0.8 to 12.0 +/- 1.4 mmHg in VE animals and from 3.3 +/- 0.4 to 5.2 +/- 0.7 mmHg in antidiuretic rats after RPP was varied from 100 to 150 mmHg. The pressure-natriuretic response of the antidiuretic rats was blunted compared with that observed in the VE rats. Decapsulation of the kidney in VE rats lowered RIHP and reduced, but did not eliminate, the pressure-natriuretic response. To determine whether this residual response was related to changes in interstitial pressure in the medulla, cortical (CIHP) and medullary interstitial hydrostatic pressures (MIHP) were simultaneously measured in VE rats with an intact or decapsulated kidney. In control rats CIHP and MIHP were similar at all levels of RPP studied. In rats with the renal capsule removed MIHP was higher than CIHP and rose significantly from 6.7 +/- 0.8 to 9.2 +/- 0.8 mmHg when RPP was varied from 100 to 150 mmHg. These results indicate that pressure diuresis and natriuresis is accompanied by changes in RIHP and the response is modulated by the basal level of RIHP. These findings suggest that changes in MIHP may serve as an intrarenal signal for this response.
Effect of diabetic hyperglycemia and other sugars on
plasma dopamine-beta-hydroxylase activity.
Munoz
A, Serrano
C, García-Estan
J, Quesada
T, Miras
Portugal MT
Diabetes 1984 Dec 33:12 1127-32
The plasma glycoprotein, dopamine-beta-hydroxylase (DBH), is present
in markedly increased amounts in experimental, streptozocin (STZ)-diabetic
rats, reaching a maximum at about the first week and maintaining a plateau
for several months afterward. High glycemia values are observed simultaneously.
Insulin treatment is observed to keep the glycemia and plasma DBH activity
values at levels seen in control rats. The heterologous half-life of DBH
in STZ-diabetic rats is significantly increased compared with that of control
animals. The glucose analogue, 2-deoxy-D-glucose, has a similar effect
on plasma DBH activity levels, eliciting high glycemia values. In STZ-diabetic
animals, this increase is more significant, as if it were the additive
effect of the two sugars. Other sugars that can compete for glycoprotein
catabolic receptors can also modulate the plasma DBH activity levels. The
lack of effect of galactose on DBH levels, together with the induced increase
of DBH by alpha-methyl-D-mannoside and, to a lesser extent, by inulin,
suggest an important rate for the mannose/glucose/N-acetyl glucosamine/fructose
receptor in the catabolic clearance of DBH from plasma and explain the
abnormal values seen for DBH in diabetes mellitus.