Converting-enzyme inhibition abolishes polydipsia induced by dietary NaCl and K depletion

1990 ◽  
Vol 258 (5) ◽  
pp. F1164-F1172
Author(s):  
A. J. McKay ◽  
C. D. Poirier ◽  
L. N. Peterson
Keyword(s):  
Water Intake ◽  
Enzyme Inhibitor ◽  
Pressor Response ◽  
Plasma Renin ◽  
High Water ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Daily Water Intake ◽  
High Water Intake ◽  
Converting Enzyme Inhibition

The present studies were designed to test the hypothesis that angiotensin II (ANG II) mediates nonosmotic thirst in animals fed the low-NaCl K-free diet by preventing the increased generation of ANG II using the converting-enzyme inhibitor, enalapril. Animals were fed either a control salt or low-NaCl K-free diet and were treated with or without enalapril. Water intake in rats fed the low-NaCl K-free diet increased more than twofold on day 3 and remained elevated over the 10-day period of study. Treatment with enalapril (40 mg.kg-1.day-1) 1) prevented the striking rise in plasma renin activity in rats fed the low-NaCl K-free diet, 2) led to complete blockade of the pressor response to a 50-ng injection of angiotensin I but not ANG II, 3) did not affect daily water intake in rats consuming the control salt diet, 4) did not reduce basal water intake in rats fed the low-NaCl K-free diet below values measured in control animals, and 5) did not abolish water intake in response to osmotic stimulation. However, enalapril treatment abolished the increase in water intake that occurs in animals fed the low-NaCl K-free diet. In a double crossover study using two groups of rats fed the low-NaCl K-free diet, enalapril prevented increased water intake in rats initially fed the low-NaCl K-free diet and rapidly inhibited increased water intake in rats fed the low-NaCl K-free diet after the high water intake had been established.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ANG II receptor antagonist on albuminuria and renal function in passive Heymann nephritis

1992 ◽  
Vol 263 (2) ◽  
pp. F311-F318
Author(s):  
F. N. Hutchinson ◽  
S. K. Webster
Keyword(s):  
Blood Pressure ◽  
Receptor Antagonist ◽  
Enzyme Inhibitor ◽  
Pressor Response ◽  
Plasma Renin ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Heymann Nephritis

Angiotensin-converting enzyme inhibitors reduce albuminuria in nephrotic subjects, but the hormonal mechanism of this effect is not known. To determine whether specific inhibition of angiotensin (ANG) II activity would decrease albuminuria as occurs after converting enzyme inhibition, rats with passive Heymann nephritis received enalapril or the ANG II receptor antagonist losartan (6 mg.kg-1.day-1) for 4 days. Enalapril reduced both albuminuria (from 583 +/- 53 to 286 +/- 55 mg/day, P less than 0.001) and the fractional clearance of albumin (FCAlb) each day after starting treatment but did not affect glomerular filtration rate (GFR). Losartan reduced albuminuria significantly only after 4 days of treatment, but this value was not different from controls. GFR significantly increased with losartan (from 1.24 +/- 0.09 to 1.73 +/- 0.21 ml/min, P less than 0.05) so that FCAlb was reduced (from 0.0134 +/- 0.0027 to 0.0080 +/- 0.0018, P less than 0.05). Blood pressure decreased only in the enalapril group. Although plasma renin activity increased and the pressor response to ANG I was inhibited by both enalapril and losartan, suggesting effective peripheral blockade of ANG II activity, a third group of nephrotic rats was treated with losartan (18 mg.kg-1.day-1) to ensure that adequate ANG II blockade was achieved. Blood pressure decreased 10 mmHg, GFR increased from 1.35 +/- 0.14 to 1.79 +/- 0.12 ml/min (P less than 0.01), but albuminuria and FCAlb did not change. Urinary total kallikrein excretion was increased only in nephrotic rats treated with enalapril. Although both enalapril and losartan reduce ANG II activity, only the converting enzyme inhibitor reduces albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of angiotensin II in water intake of genetically polydipsic mice

1991 ◽  
Vol 260 (6) ◽  
pp. R1152-R1158 ◽  
Author(s):  
T. Katafuchi ◽  
Y. Hattori ◽  
I. Nagatomo ◽  
K. Koizumi ◽  
E. Silverstein
Keyword(s):  
Angiotensin Ii ◽  
Food Intake ◽  
Water Intake ◽  
Enzyme Inhibitor ◽  
Dark Period ◽  
Plasma Renin ◽  
Ang Ii ◽  
Arterial Blood ◽  
Daily Water Intake ◽  
Reduced Drinking

The involvement of angiotensin II (ANG II) in the genetic polydipsia of the STR/N strain of mice was investigated. Daily water intake of the polydipsic inbred STR/N of both sexes ranged between five and eight times that of nonpolydipsic controls: STR/1N, a mutant of the STR/N, and Swiss-Webster (S/W) mice. Nevertheless the diurnal pattern of drinking was maintained in the STR/N. There was no difference in daily food intake, arterial blood pressure, and plasma renin activity among the three groups. Drinking responses to 48 h of water deprivation were not significantly different between the polydipsic mice and their control groups. Captopril, an angiotensin I converting-enzyme inhibitor, injected subcutaneously just before the dark period, reduced drinking for 6 h in the polydipsic strain only. Food intake of all three groups of mice was not affected. Similarly the ANG II antagonist saralasin, [Sar1,-Ile8]ANG II, injected into the lateral cerebroventricle just before the dark period, significantly reduced water intake for 6 h after injection in the polydipsic mice only. Intracerebroventricular injection of ANG II increased drinking in the nondeprived controls but not in the polydipsic mice. These findings suggest that the polydipsia in the STR/N mice may involve, at least in part, the ANG II system in the brain.

Role of arteria baroreceptor input on thirst and urinary responses to intracerebroventricular angiotensin II

1993 ◽  
Vol 265 (3) ◽  
pp. R591-R595 ◽  
Author(s):  
R. L. Thunhorst ◽  
S. J. Lewis ◽  
A. K. Johnson
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Water Intake ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Arterial Blood ◽  
Endogenous Formation

Intracerebroventricular (icv) infusion of angiotensin II (ANG II) in rats elicits greater water intake under hypotensive, compared with normotensive, conditions. The present experiments used sinoaortic baroreceptor-denervated (SAD) rats and sham-operated rats to examine if the modulatory effects of arterial blood pressure on water intake in response to icv ANG II are mediated by arterial baroreceptors. Mean arterial blood pressure (MAP) was raised or lowered by intravenous (i.v.) infusions of phenylephrine (1 or 10 micrograms.kg-1 x min-1) or minoxidil (25 micrograms.kg-1 x min-1), respectively. The angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) was infused i.v. to prevent the endogenous formation of ANG II during testing. Urinary excretion of water and solutes was measured throughout. Water intake elicited by icv ANG II was inversely related to changes in MAP. Specifically, rats drank more water in response to icv ANG II when MAP was reduced by minoxidil but drank less water when MAP was elevated by phenylephrine. The influence of changing MAP on the icv ANG II-induced drinking responses was not affected by SAD. These results suggest that the modulatory effects of arterial blood pressure on icv ANG II-induced drinking can occur in the absence of sinoaortic baroreceptor input.

scholarly journals Effects of hypotension and fluid depletion on central angiotensin-induced thirst and salt appetite

2001 ◽  
Vol 281 (5) ◽  
pp. R1726-R1733 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Alan Kim Johnson
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Water Intake ◽  
Enzyme Inhibitor ◽  
Salt Appetite ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Nacl Solution ◽  
Subcutaneous Injections ◽  
Sodium Ingestion ◽  
Vasodilator Drug

We examined the effects of hypotension and fluid depletion on water and sodium ingestion in rats in response to intracerebroventricular infusions of ANG II. Hypotension was produced by intravenous infusion of the vasodilator drug minoxidil (25 μg · kg−1 · min−1) concurrently with the angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) to prevent endogenous ANG II formation. Hypotension increased water intake in response to intracerebroventricular ANG II (30 ng/h) but not intake of 0.3 M NaCl solution and caused significant urinary retention of water and sodium. Acute fluid depletion was produced by subcutaneous injections of furosemide (10 mg/kg body wt) either alone or with captopril (100 mg/kg body wt sc) before intracerebroventricular ANG II (15 or 30 ng/h) administration. Fluid depletion increased water intake in response to the highest dose of intracerebroventricular ANG II but did not affect saline intake. In the presence of captopril, fluid depletion increased intakes of both water and saline in response to both doses of intracerebroventricular ANG II. Because captopril administration causes hypotension in fluid-depleted animals, the results of the two experiments suggest that hypotension in fluid-replete animals preferentially increases water intake in response to intracerebroventricular ANG II and in fluid-depleted animals increases both salt and water intake in response to intracerebroventricular ANG II.

Central infusion of the AT1 receptor antagonist losartan inhibits thirst but not sodium appetite in cattle

1997 ◽  
Vol 272 (6) ◽  
pp. R1940-R1945 ◽  
Author(s):  
J. R. Blair-West ◽  
D. A. Denton ◽  
M. J. McKinley ◽  
R. S. Weisinger
Keyword(s):  
Water Intake ◽  
Salt Intake ◽  
Sodium Intake ◽  
High Water ◽  
Salt Appetite ◽  
Ang Ii ◽  
Sodium Depletion ◽  
Water Restriction ◽  
Sodium Appetite ◽  
High Water Intake

Experiments in cattle compared the effects of intracerebroventricular (i.c.v.) infusions of losartan and PD-123319 on water intake caused by water restriction, i.c.v. infusion of hypertonic NaCl, or i.c.v. infusion of angiotensin II (ANG II). The effects of these receptor antagonists on sodium intake caused by sodium depletion were also examined. Losartan infusion caused dose-dependent inhibition of the high water intake caused by the physiological stimulus of water restriction or by ANG II infusion but did not affect salt appetite. PD-123319 infused at equimolar or greater (in ANG II experiments) doses did not affect water intake or salt intake due to sodium depletion. The results of these i.c.v. infusion experiments confirm our earlier proposal that the physiological regulation of water intake in cattle may be mediated by ANG II acting centrally via AT1 receptors. The dose of losartan that inhibited thirst in cattle did not inhibit sodium appetite, nor did an equimolar dose of PD-123319.

Angiotensin-converting enzyme inhibition and Na appetite: microbehavioral analysis and nycthemeral physiology

1993 ◽  
Vol 265 (1) ◽  
pp. R7-R13 ◽  
Author(s):  
N. E. Rowland ◽  
T. M. Nicholson ◽  
J. C. Smith
Keyword(s):  
Enzyme Inhibitor ◽  
Chronic Administration ◽  
Plasma Renin ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Sprague Dawley ◽  
Sodium Appetite ◽  
Angiotensin I Converting Enzyme ◽  
Sprague Dawley Rats ◽  
Converting Enzyme Inhibition

The present experiments describe a marked nycthemeral rhythm in both the appetite for 0.3 M NaCl solution and components of the renin-angiotensin-aldosterone axis stimulated in Sprague-Dawley rats by chronic administration of enalapril, an angiotensin I-converting enzyme inhibitor. Continuous recording of water, NaCl, and food intakes shows that the sodium appetite is manifest as discrete bouts of salt ingestion in temporal proximity to meals and is partially independent of water bouts. In particular, salt bouts occur without water bouts in the late afternoon of a 12:12-h light-dark cycle and continue periprandially with water bouts during the night. Intake of all three commodities is minimal in the morning. In a second experiment, it was determined that plasma renin activity (PRA) was maximally elevated by chronic enalapril in the daytime and that plasma aldosterone was reduced by enalapril but continued to show nycthemeral rhythm peaking in the afternoon. The concurrent maxima in PRA and aldosterone in the afternoon in enalapril-treated rats thus coincides with NaCl intake in the absence of water intake.

scholarly journals Estrogen protects transgenic hypertensive rats by shifting the vasoconstrictor-vasodilator balance of RAS

1997 ◽  
Vol 273 (6) ◽  
pp. R1908-R1915 ◽  
Author(s):  
K. Bridget Brosnihan ◽  
Ping Li ◽  
Detlev Ganten ◽  
Carlos M. Ferrario
Keyword(s):  
Replacement Therapy ◽  
Estrogen Replacement Therapy ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Cardiovascular Responses ◽  
Estrogen Treatment ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Estrogen Replacement

In pursuit of the hypothesis that estrogen shifts the vasoconstrictor-vasodilator balance of the renin-angiotensin system, we investigated the cardiovascular responses to administration of angiotensin-(1—7) [ANG-(1—7)] and angiotensin II (ANG II) in female transgenic (mRen2)27-positive [Tg(+)] and -negative [Tg(−)] rats in the presence and absence of 3 wk of estrogen replacement therapy. Fifty-three female Tg(−) and Tg(+) rats were oophorectomized and received either 17β-estradiol (1.5 mg/rat sc for 3 wk) or vehicle. At the end of 3 wk of estrogen treatment, mean blood pressure was lowered in freely moving chronically cannulated Tg(+) (159 ± 4 vs. 145 ± 5 mmHg, P < 0.05) and Tg(−) (119 ± 4 vs. 108 ± 2 mmHg, P < 0.05) rats. Moreover, the magnitude of the depressor component of the biphasic response to ANG-(1—7) was significantly enhanced in estrogen-treated Tg(+) rats, whereas the pressor component to ANG-(1—7) was attenuated in both Tg(+) and Tg(−) rats. Estrogen replacement significantly attenuated the pressor response to ANG II in both Tg(+) and Tg(−) rats. In addition, estrogen replacement therapy significantly reduced plasma ANG-converting enzyme activity in association with a reduction in circulating levels of ANG II. Tissue levels (kidney and aorta) of ANG-converting enzyme were also reduced with chronic estrogen replacement therapy. On the other hand, estrogen augmented the levels of plasma ANG-(1—7) in Tg(+) animals. Plasma renin activity was unchanged with estrogen treatment. These findings provide the first evidence demonstrating that estrogen is protective against hypertension, possibly by amplifying the vasodilator contributions of ANG-(1—7), while reducing the formation and vasoconstrictor actions of ANG II.

Mechanism of antihypertensive effect of potassium depletion in renovascular hypertension

1988 ◽  
Vol 255 (5) ◽  
pp. H1181-H1187
Author(s):  
C. R. Nolan ◽  
S. L. Linas
Keyword(s):  
Renovascular Hypertension ◽  
Antihypertensive Effect ◽  
Enzyme Inhibitor ◽  
Pressor Response ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitor ◽  
Total Binding ◽  
Receptor Number ◽  
K Depletion

K depletion (KD) prevents the development of hypertension in two-kidney, one-clip renovascular, hypertension [mean arterial pressure: 110 +/- 5 (KD) vs. 142 +/- 3 mmHg in potassium replete (KR); P less than 0.001]. The protective effect of KD is associated with a 60% decrease in angiotensin II (ANG II) pressor responsiveness and a 40% decrease in ANG II binding to mesenteric artery particles from rats with renovascular hypertension (receptor number 117 +/- 16 in KD vs. 165 +/- 14 fmol/mg protein in KR, P less than 0.05). To determine whether decreases in binding could account for decreases in ANG II pressor responsivity, we measured ANG II binding after bilateral nephrectomy or sustained administration of converting-enzyme inhibitor. Both maneuvers resulted in increases in binding, such that total binding and receptor number were greater than in comparably treated KR rats; e.g., after nephrectomy, receptor number was 215 +/- 26 in KD vs. 98 +/- 12 fmol/mg protein in KR, (P less than 0.01). Despite increased binding, the pressor response to ANG II in KD rats, which were nephrectomized or treated with converting-enzyme inhibitor, was still reduced by 50% compared with comparably treated KR rats. To determine whether the decreased ANG II pressor responsivity of KD was caused by cellular K depletion or to increases in ANG H induced by KD, we administered K to KD, ANG II-deficient rats. ANG II pressor responsivity increased, and total binding and receptor number decreased (KD, ANG II- deficient 246 +/ 22 fmol/mg protein; KD, ANG II-deficient + K 91 +/ 16 fmol/mg protein; P less than 0.005) with K.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for the Local Occurrence of Angiotensin II in Rat Kidney and its Modulation by Dietary Sodium Intake and Converting Enzyme Blockade

1979 ◽  
Vol 57 (2) ◽  
pp. 173-179 ◽  
Author(s):  
F. A. O. Mendelsohn
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Enzyme Inhibitor ◽  
Sodium Intake ◽  
Rat Kidney ◽  
Plasma Renin ◽  
Renin Activity ◽  
Dietary Sodium ◽  
Ang Ii ◽  
Converting Enzyme

1. Angiotensin II (ANG II) was measured in acid-ethanol homogenates of rapidly frozen rat kidneys by a method involving ion-exchange and immunoadsorbent purification of peptides before radioimmunoassay. 2. Concentrations of ANG II found in kidney were 10–20 times that in plasma. 3. Perfusion of the kidneys via the renal artery with isotonic sodium chloride solution or with disodium EDTA solution did not alter the concentrations of intrarenal ANG II. 4. Animals fed on a sodium-deficient diet for 8 days had markedly higher concentrations of intrarenal ANG II, plasma renin activity and kidney renin concentration than sodium-replete animals. 5. After oral sodium loading for 3 weeks, rats had suppressed plasma renin activity and kidney renin concentration but unchanged intrarenal ANG II when compared with animals on a normal sodium intake. 6. One hour after the administration of a converting enzyme inhibitor (SQ 20881) plasma renin activity was elevated, kidney renin concentration unchanged and intrarenal ANG II was depressed. 7. These results demonstrate the presence of ANG II in the extravascular compartment of the kidney. They further suggest that its quantity is influenced by sodium intake and that angiotensin I converting enzyme is essential for its formation.

Effect of angiotensin-converting enzyme inhibitor on salt appetite and thirst of BALB/c mice

1990 ◽  
Vol 259 (4) ◽  
pp. R736-R740 ◽  
Author(s):  
R. S. Weisinger ◽  
J. R. Blair-West ◽  
D. A. Denton ◽  
M. McBurnie ◽  
F. Ong ◽  
...  
Keyword(s):  
Food Intake ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Converting Enzyme Inhibitor ◽  
Water Intake ◽  
Low Dose ◽  
Enzyme Inhibitor ◽  
High Dose ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitor

The role of angiotensin II (ANG II) in Na-depletion-induced Na appetite of mice was investigated. Intraperitoneal injection of the angiotensin-converting enzyme inhibitor captopril at 1.7 mg/mouse (high dose) decreased the Na intake of the Na-depleted (furosemide-treated) mice by 80-85%. The decrease in Na intake was restored to the initial level by concurrent subcutaneous infusion of ANG II. High dose of captopril also decreased the Na intake of fluid-deprived, Na-depleted mice. High dose of captopril did not alter water intake in any of the four conditions examined, i.e., in fluid-replete, Na-depleted, water-deprived, or fluid-deprived, Na-depleted mice. Low dose of captopril (1.7 microgram/mouse) tended to or significantly enhanced Na intake of Na-depleted mice. Low dose of captopril, however, did not enhance water intake in any of the conditions examined. Both high- and low-dose captopril treatment decreased food intake in water-deprived mice, whether or not the mice were Na depleted as well. The addition of captopril (0.1 or 1.0 mg/ml) to the drinking water did not influence Na or food intake. Water intake was enhanced during treatment with the low but not with the high dose of captopril. The results are consistent with the proposition that ANG II is involved in the Na appetite of Na-depleted mice. ANG II does not appear to have a role in water intake of Na-depleted or water-deprived mice, but neural mechanisms in which angiotensin has a role may influence food intake of water-deprived mice.

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