scholarly journals Salt-sensitive hypertension in ANP knockout mice: potential role of abnormal plasma renin activity

1998 ◽  
Vol 274 (1) ◽  
pp. R255-R261 ◽  
Author(s):  
L. G. Melo ◽  
A. T. Veress ◽  
C. K. Chong ◽  
S. C. Pang ◽  
T. G. Flynn ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Knockout Mice ◽  
Salt Intake ◽  
Plasma Renin ◽  
Peptide Hormone ◽  
Hypotensive Effect ◽  
The State ◽  
Renin Activity ◽  
Arterial Blood ◽  
Salt Sensitive Hypertension

Atrial natriuretic peptide (ANP), a peptide hormone produced by the heart, exerts a chronic hypotensive effect. Knockout mice with a homozygous disruption of the pro-ANP gene (−/−) are incapable of producing ANP and are hypertensive relative to their wild-type (+/+) siblings. Previous studies showed that arterial blood pressure (ABP) was further increased in conscious −/− mice kept for 2 wk on 2% salt, but not in anesthetized −/− mice after 1 wk on 8% salt. To determine whether inconsistencies in observed effects of salt on ABP of −/− mice are due to duration of increased salt intake and/or the state of consciousness of the animals, we measured ABP from an exteriorized carotid catheter during and after recovery from anesthesia with ketamine-xylazine in adult +/+ and −/− mice kept on low (LS; 0.008% NaCl)- or high (HS; 8% NaCl)-salt diets for 3–4 wk. Conscious ABP ± SE (mmHg) of +/+ mice did not differ significantly on either diet (HS, 113 ± 3; LS, 110 ± 5). However, on HS diet −/− mice had significantly higher ABP (135 ± 3; P < 0.001) than both −/− (115 ± 2) and +/+ (110 ± 5) mice on LS diet. Anesthesia decreased ABP in all groups, but the genotype- and diet-related differences were preserved. Plasma renin activity (PRA, ng ANG I ⋅ ml−1 ⋅ h−1) in blood collected at termination of experiment was appropriately different on the 2 diets in +/+ mice (HS, 4.9 ± 1.9; LS, 21 ± 2.8). However, PRA failed to decrease in −/− mice on HS diet (HS, 18 ± 2.9; LS, 19 ± 3.7). Independent of genotype, concentration of endothelin-1 (ET-1, pg/mg protein) and endothelial constitutive NOS (ecNOS, density/100 μg protein) was significantly elevated in kidneys of mice fed on HS diet (ET-1 −/−, 31 ± 4.7 and +/+, 32 ± 4.1; ecNOS −/−, 160 ± 19 and +/+, 156 ± 19) compared with mice fed on LS diet (ET-1 −/−, 19 ± 1.9 and +/+, 21 ± 1.8; ecNOS −/−, 109 ± 13 and +/+, 112 ± 18). We conclude that, regardless of the state of alertness, −/− mice develop salt-sensitive hypertension after prolonged feeding on HS, in part due to their inability to reduce PRA, whereas the specific renal upregulation of ecNOS and ET-1 in response to HS intake may be an ANP-independent adaptive adjustment aimed at improving kidney function and counteracting the pressor effect of salt.

VARIATIONS IN PLASMA RENIN ACTIVITY AND URINARY ALDOSTERONE EXCRETION IN NORMAL SUBJECTS AFTER SALT RESTRICTION AND ACUTE PITUITARY INHIBITION WITH 6-DEHYDRO-16-METHYLENE HYDROCORTISONE

1971 ◽  
Vol 67 (1) ◽  
pp. 159-173
Author(s):  
A. Peytremann ◽  
R. Veyrat ◽  
A. F. Muller
Keyword(s):  
Plasma Renin Activity ◽  
Salt Intake ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Inhibitory Effect ◽  
Renin Activity ◽  
Sodium Balance ◽  
Experimental Conditions ◽  
Salt Restriction ◽  
Aldosterone Production

ABSTRACT Variations in plasma renin activity and urinary aldosterone excretion were studied in normal subjects submitted to salt restriction and simultaneous inhibition of ACTH production with a new synthetic steroid, 6-dehydro-16-methylene hydrocortisone (STC 407). At a dose of 10 mg t. i. d. this preparation exerts an inhibitory effect on the pituitary comparable to that of 2 mg of dexamethasone. In subjects maintained on a restricted salt intake, STC 407 does not delay the establishment of an equilibrium in sodium balance. The increases in endogenous aldosterone production and in plasma renin activity are also similar to those seen in the control subjects. A possible mineralocorticoid effect of STC 407 can be excluded. Under identical experimental conditions, the administration of dexamethasone yielded results comparable to those obtained with STC 407.

Enhancement of the Antihypertensive Effect of Hydrochlorothiazide in Dogs after Suppression of Renin Release by Beta-Adrenergic Blockade

1975 ◽  
Vol 48 (2) ◽  
pp. 147-151
Author(s):  
C. S. Sweet ◽  
M. Mandradjieff
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Arterial Blood Pressure ◽  
Antihypertensive Effect ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Antihypertensive Activity ◽  
Adrenergic Blockade ◽  
Arterial Blood

1. Renal hypertensive dogs were treated with hydrochlorothiazide (8−2 μmol/kg or 33 μmol/kg daily for 7 days), or timolol (4.6 μmol/kg daily for 4 days), a potent β-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.

Salt-sensitive hypertension in ANP knockout mice is prevented by AT1 receptor antagonist losartan

1999 ◽  
Vol 277 (3) ◽  
pp. R624-R630 ◽  
Author(s):  
Luis G. Melo ◽  
Anthony T. Veress ◽  
Chee K. Chong ◽  
Uwe Ackermann ◽  
Harald Sonnenberg
Keyword(s):  
Receptor Antagonist ◽  
Knockout Mice ◽  
Plasma Renin ◽  
Plasma Catecholamine ◽  
Ang Ii ◽  
Dietary Salt ◽  
Water Control ◽  
Dietary Regimen ◽  
Arterial Blood ◽  
Salt Sensitive Hypertension

Mice harboring a functional deletion of the pro-atrial natriuretic peptide (ANP) gene (−/−) develop salt-sensitive hypertension relative to their wild-type (+/+) counterparts after prolonged (>1 wk) maintenance on high-salt (HS, 8% NaCl) diet. We reported recently that the sensitization of arterial blood pressure (ABP) to dietary salt in the −/− mice is associated with failure to downregulate plasma renin activity. To further characterize the role and mechanism of ANG II in the sensitization of ABP to salt in the ANP “knockout” mice, we measured ABP, heart rate (HR), and plasma catecholamine and aldosterone concentrations in −/− and +/+ mice maintained on HS for 4 wk and treated with daily injections of AT1 receptor antagonist DuP-753 (losartan) or distilled water (control). Daily food and water intake and fluid and electrolyte excretion were also measured during the first and last weeks of the dietary regimen. Cumulative urinary excretion of fluid and electrolytes did not differ significantly between genotypes and was not altered by chronic treatment with losartan. Basal ABP and HR were significantly elevated in control −/− mice compared with control +/+ mice. Losartan did not affect ABP or HR in +/+ mice, but reduced ABP and HR in the −/− mice to the levels in the +/+ mice. Total plasma catecholamine was elevated by approximately ten-fold in control −/− mice compared with control +/+ mice. Losartan reduced plasma catecholamine concentration significantly in −/− mice and abrogated the difference in plasma catecholamine between −/− and +/+ mice on HS diet. Plasma aldosterone did not differ significantly between genotypes and was not altered by losartan. We conclude that salt sensitivity of ABP in ANP knockout mice is mediated, at least in part, by a synergistic interaction between ANG II and sympathetic nerve activity.

Pharmacological and genetic evidence that cathepsin B is not the physiological activator of rodent prorenin

2010 ◽  
Vol 391 (12) ◽  
Author(s):  
M. David Percival ◽  
Sylvie Toulmond ◽  
Nathalie Coulombe ◽  
Wanda Cromlish ◽  
Sylvie Desmarais ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Cathepsin B ◽  
Plasma Renin ◽  
Renin Activity ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Arterial Blood ◽  
Gene Compensation

Abstract Renin is the first enzyme in the renin-angiotensin-aldosterone system which is the principal regulator of blood pressure and hydroelectrolyte balance. Previous studies suggest that cathepsin B is the activator of the prorenin zymogen. Here, we show no difference in plasma renin activity, or mean arterial blood pressure between wild-type and cathepsin B knockout mice. To account for potential gene compensation, a potent, selective, reversible cathepsin B inhibitor was developed to determine the role of cathepsin B on prorenin processing in rats. Pharmacological inhibition of cathepsin B in spontaneously hypertensive and double transgenic rats did not result in a reduction in renal mature renin protein levels or plasma renin activity. We conclude that cathepsin B does not play a significant role in this process in rodents.

Plasma renin activity responses to graded decreases in renal perfusion pressure in fetal and newborn lambs

1992 ◽  
Vol 262 (3) ◽  
pp. R524-R529 ◽  
Author(s):  
N. D. Binder ◽  
D. F. Anderson
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Perfusion Pressure ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Renin Activity ◽  
Renal Perfusion Pressure ◽  
Arterial Blood ◽  
The Right ◽  
The Relationship

We examined the relationship between acute reductions in renal perfusion pressure, as approximated by femoral arterial blood pressure, and plasma renin activity in the uninephrectomized fetal lamb. Renal perfusion pressure was reduced and maintained at a constant value by controlled partial occlusion of the aorta above the renal artery. After 15 min of reduced blood pressure, blood samples were taken for determination of plasma renin activity. This protocol was performed 22 times in 11 fetal lambs. Additionally, three of the fetuses were delivered by cesarean section and studied as newborns for the first week of life. In the fetus, there was a linear relationship between log plasma renin activity and femoral arterial blood pressure (P less than 0.01). After birth, the relationship still existed, although it was shifted to the right (P less than 0.0001). We conclude that there is a significant relationship between plasma renin activity and renal perfusion pressure in the fetal lamb, and as early as 1 day after birth, this relationship shifts to the right in the newborn lamb.

Suppression of renin release by antagonism of endogenous opiates in the dog

1986 ◽  
Vol 250 (4) ◽  
pp. R633-R637
Author(s):  
J. E. Szilagyi ◽  
J. Chelly ◽  
M. F. Doursout
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Endogenous Opioids ◽  
Renin Activity ◽  
Renin Release ◽  
Endogenous Opioid ◽  
Endogenous Opiates ◽  
Arterial Blood ◽  
Before And After ◽  
Arterial Constriction

The influence of blockade of endogenous opioids on the release of renin due to partial renal arterial constriction was determined acutely and chronically in unilaterally nephrectomized dogs. In acute preparations changes in plasma renin activity, arterial blood pressure, and heart rate were determined after 15 min of 60% renal arterial constriction before and after administration of either a saline vehicle, the opiate antagonist naloxone (0.05 mg/kg), or morphine (2 mg/kg). Acute antagonism of endogenous opiates abolished the increase in plasma renin activity and mean arterial pressure associated with renal arterial constriction. Repeated renal arterial constrictions in saline- or morphine-treated animals did not alter the humoral or hemodynamic responses. In chronic preparations long-term naloxone infusion attenuated the development of renovascular hypertension and diminished the increase in plasma renin activity. These data suggest that endogenous opioid peptides are modulators in the control of renin release and may be important participants in the pathogenesis of hypertension.

Effects of blood viscosity on plasma renin activity and renal hemodynamics

1986 ◽  
Vol 250 (1) ◽  
pp. F40-F46 ◽  
Author(s):  
S. Simchon ◽  
R. Y. Chen ◽  
R. D. Carlin ◽  
F. C. Fan ◽  
K. M. Jan ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Blood Viscosity ◽  
Plasma Renin ◽  
Plasma Viscosity ◽  
Renal Hemodynamics ◽  
Renin Activity ◽  
Sodium Pentobarbital ◽  
Coefficient Of Correlation ◽  
Arterial Blood ◽  
Renal Vascular

The effects of alterations in apparent blood viscosity on renal hemodynamics and plasma renin activity (PRA) were studied in dogs anesthetized with sodium pentobarbital. Blood viscosity was altered isovolemically either by changes in hematocrit (Hct) or by an increase in plasma viscosity (dextran administration). Arterial blood pressure and renal blood flow (RBF) remained relatively constant when apparent blood viscosity was elevated by changes in Hct or plasma viscosity. Thus the hyperviscosity of blood was associated with a decrease of renal vascular hindrance, resulting in an essentially unchanged renal flow resistance. The decrease in renal vascular hindrance may result from renal vasodilation. In hyperviscosity induced with dextran, the increase in PRA correlates linearly with the decrease in renal vascular hindrance, with a coefficient of correlation of 0.968 (P less than 0.005). The increase in PRA that resulted when Hct was raised from 25 to 55% also can be correlated linearly with the decrease in renal vascular hindrance, with a coefficient of correlation of 0.953 (P less than 0.005). These results suggest that the decrease in renal vascular hindrance in response to a rise in apparent blood viscosity leads to an increase in PRA.

Hormonal responses to synthetic atrial natriuretic peptide in patients on regular hemodialysis

1988 ◽  
Vol 119 (2) ◽  
pp. 257-262 ◽  
Author(s):  
Sadao Nakajima ◽  
Hiromichi Suzuki ◽  
Yo Kageyama ◽  
Takashi Takita ◽  
Takao Saruta
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Renin Activity ◽  
Arterial Blood ◽  
Sympathetic Nervous ◽  
Regular Hemodialysis

Abstract. The effects of atrial natriuretic peptide (ANP) on mean arterial blood pressure, heart rate, plasma renin activity, aldosterone, cortisol, norepinephrine, epinephrine and arginine vasopressin were studied in 6 anuric subjects receiving regular hemodialysis. An iv bolus injection of 8 nmol of ANP followed by infusion at 32 pmol·kg−1·min−1 for 1 h in the pre- and posthemodialysis period was performed. Basal plasma ANP was higher before than after hemodialysis. ANP administration produced a reduction in mean arterial blood pressure accompanied by an elevation of norepinephrine and of plasma renin activity (from 2.49 ± 0.52 to 3.39 ± 0.85 nmol·l−1·h−1 predialysis and from 2.78 ± 0.71 to 3.15 ± 0.86 nmol·l−1·h−1 postdialysis, respectively, mean ± sem; P < 0.05). Plasma aldosterone and cortisol were significantly decreased. Plasma epinephrine and AVP remained unchanged. These hemodynamic and hormonal changes were similar in the pre- and the postdialysis period. These results suggest that 1) ANP causes a fall in mean arterial blood pressure, which in turn induces reflex tachycardia and activation of the sympathetic nervous system without diuresis; 2) the activated sympathetic nervous system as reflected in elevation of plasma norepinephrine may increase plasma renin activity; 3) reduced plasma aldosterone is not influenced by enhancement of the reninangiotensin system; therefore, 4) reduction of plasma aldosterone as well as cortisol is probably due to direct action of ANP, and finally 5) AVP had no direct relation with ANP administration.

scholarly journals Role of prostanoids in regulation of the renin-angiotensin-aldosterone system by salt intake

2002 ◽  
Vol 283 (2) ◽  
pp. F294-F301 ◽  
Author(s):  
Klaus Höcherl ◽  
Martin C. Kammerl ◽  
Karl Schumacher ◽  
Dirk Endemann ◽  
Horst F. Grobecker ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Salt Intake ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Renin Activity ◽  
Plasma Aldosterone Concentration ◽  
Low Salt ◽  
Renin Mrna ◽  
Cox 2 ◽  
Cox 1

We investigated the effect of cyclooxygenase (COX) activity on the regulation of the renin-angiotensin-aldosterone system by salt intake. Therefore, Sprague-Dawley rats were subjected to different salt diets [0.02, 0.6, and 8% NaCl (wt/wt)] and treated with the selective COX-2 inhibitor rofecoxib (10 mg · kg body wt−1 · day−1) or with ketorolac at a dose selective for COX-1 inhibition (2 mg · kg body wt−1 · day−1) for 3, 7, 14, and 21 days. Rofecoxib and ketorolac caused a similar reduction of renocortical PGE2 formation with a low-salt diet. Rofecoxib did not change plasma renin activity or renocortical renin mRNA abundance with any of the diets but clearly lowered plasma aldosterone concentration. In contrast, ketorolac delayed the increase in plasma renin activity and of renin mRNA in response to low salt intake but did not change plasma aldosterone concentration. Prolonged treatment with rofecoxib but not with ketorolac caused an upregulation of COX-2 expression while COX-1 mRNA abundance remained unchanged. These findings suggest that COX-1-derived, but not COX-2-derived, prostanoids are of relevance for the regulation of the renin system by salt intake.

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