Combined intrarenal blockade of the renin-angiotensin system in the conscious dog

1990 ◽  
Vol 258 (3) ◽  
pp. F522-F529 ◽  
Author(s):  
H. M. Siragy ◽  
N. L. Howell ◽  
M. J. Peach ◽  
R. M. Carey
Keyword(s):  
Renal Function ◽  
Enzyme Inhibitor ◽  
Renal Plasma Flow ◽  
Renin Angiotensin System ◽  
Fractional Excretion ◽  
Random Order ◽  
Sodium Balance ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Fractional Excretion Of Sodium

We produced maximal or near-maximal acute intrarenal blockade of the renin-angiotensin system (RAS) by combining inhibitors. Intrarenal infusion of the renin inhibitor, ACRIP, the converting enzyme inhibitor, teprotide, and saralasin were administered individually or combined in random order. The inhibitors were infused for 20 min in doses that did not produce systemic effects in uninephrectomized conscious dogs in sodium balance at 10 meq/day. Significant increases in urine flow rate (UV; F = 97, P less than 0.0001), urinary sodium excretion (UNaV; F = 220, P less than 0.0001), glomerular filtration rate (GFR; F = 64, P less than 0.0001), and renal plasma flow (RPF; F = 108, P less than 0.0001) were observed with each blocker, whether alone or in combination except that ACRIP alone did not alter GFR or RPF. The increase in renal function was related to the number of blockers (3 greater than 2 greater than 1). With the three blockers combined UV increased approximately sixfold (from 0.5 +/- 0.06 to 2.9 +/- 0.03 ml/min), UNaV approximately 10-fold (from 3 +/- 0.4 to 34 +/- 2.8 mueq/min), GFR from 31 +/- 2 to 49 +/- 2 ml/min, RPF from 59 +/- 1 to 120 +/- 4 ml/min, and fractional excretion of sodium from 0.06 +/- 0.01 to 0.5 +/- 0.4% (all P less than 0.001). These changes did not occur where the inhibitors were infused systemically and the changes during intrarenal blocker administration were blocked completely with co-administration of angiotensin II intrarenally. The intrarenal RAS is a potent physiological regulator of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the renin-angiotensin system in mediating the effects of posture on renal function

1996 ◽  
Vol 271 (1) ◽  
pp. R282-R288 ◽  
Author(s):  
G. A. Reinhart ◽  
T. E. Lohmeier
Keyword(s):  
Renal Function ◽  
Sodium Excretion ◽  
Renal Plasma Flow ◽  
Renin Angiotensin System ◽  
Renal Hemodynamics ◽  
Conscious Dogs ◽  
Plasma Norepinephrine ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

This study was designed to quantitate the influence of the neurohumoral activation associated with orthostatic stress on renal hemodynamics and sodium excretion and, furthermore, to determine the importance of the renin-angiotensin system in mediating these changes in renal function. Seven conscious dogs were studied while lying in the recumbent position and, subsequently, after standing in a supporting sling. Experiments were conducted under control conditions and after plasma angiotensin II (ANG II) concentration was fixed at control levels by chronic infusion of captopril (14 micrograms.kg-1.min-1) and ANG II (0.5 +/- 0.02 ng.kg-1.min-1). During control experiments, 45 min of standing increased plasma renin activity twofold, whereas mean arterial pressure, heart rate, and plasma norepinephrine concentration remained unchanged. During standing, glomerular filtration rate (GFR) and renal plasma flow (RPF) fell to 88 +/- 2 and 77 +/- 3% of recumbent values, respectively, whereas filtration fraction (FF) increased 16 +/- 1%. Additionally, urinary (UNaV) and fractional sodium excretion (FENa) decreased to 27 +/- 6 and 30 +/- 7% of recumbent values, respectively. When plasma ANG II concentration was fixed at control levels during standing, there were no significant changes in GFR, whereas increments in FF and reductions in RPF, UNaV, and FENa were attenuated by 63, 40, 30, and 33%, respectively. These data suggest that, in conscious dogs, standing in a supporting sling causes reflex activation of the sympathetic nervous and renin-angiotensin systems, eliciting reductions in GFR, RPF, and UNaV. Furthermore, ANG II contributes significantly to the effects of passive standing on renal hemodynamics and UNaV.

Blood pressure effects of renin inhibition by human renin antiserum in normotensive marmosets

1984 ◽  
Vol 246 (3) ◽  
pp. F309-F316 ◽  
Author(s):  
J. B. Michel ◽  
J. Wood ◽  
K. Hofbauer ◽  
P. Corvol ◽  
J. Menard
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Pressure Effects ◽  
Sodium Balance ◽  
New World Monkeys ◽  
Common Marmosets ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Human Renin

The effects on blood pressure of an antiserum against pure human kidney renin were studied in conscious and anesthetized (pentobarbital, 24 mg X kg-1 i.p.) small new world monkeys (common marmosets). The antiserum inhibited the enzymatic activity of renin by 50% in a dilution of 1:45,000 in marmoset and 1:50,000 in human plasma. The antiserum (0.2 ml i.v.) decreased blood pressure in conscious marmosets on normal sodium intake by 15 +/- 5 (SD) mmHg and after salt depletion by 31 +/- 13 mmHg. A converting enzyme inhibitor (teprotide, 2 mg X kg-1 i.v.) induced a comparable fall in blood pressure: -16 +/- 10 and -30 +/- 10 mmHg, respectively. Similar effects were observed on blood pressure of anesthetized marmosets. The correlation between pretreatment plasma renin concentration and the maximum fall in blood pressure was significant and identical for the experiments with antiserum and teprotide. These results demonstrate that antisera against human renin can be used for the specific blockade of the renin-angiotensin system in primates. In normotensive marmosets the renin-angiotensin system participates in the maintenance of blood pressure, to a degree depending on the state of sodium balance.

Role of endogenous endothelin on renal functions in rats

1991 ◽  
Vol 260 (1) ◽  
pp. F34-F38
Author(s):  
K. Yamada ◽  
S. Yoshida
Keyword(s):  
Sodium Excretion ◽  
Salt Intake ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Sodium Balance ◽  
High Salt Intake ◽  
Fractional Excretion Of Sodium

This study was conducted to determine the involvement of endogenous endothelin (ET), a novel potent vasoconstricting peptide, in systemic and renal hemodynamics and in the renin-angiotensin system by inhibiting ET action via infusion of a specific ET antiserum at a time of altered sodium balance. Infusion of 1:50 diluted ET antiserum, which completely inhibited renal vasoconstriction by the exogenously administered ET (0.25 to 1.0 nmol/kg), caused an increase in urinary sodium excretion and fractional excretion of sodium and a decrease in plasma renin concentration without significant changes in blood pressure, heart rate, glomerular filtration rate, renal plasma flow, and urine volume compared with the values with nonimmune serum in conscious rats fed a low-salt diet. A time control study showed no significant changes in all parameters. These results suggest that the state of low- compared to high-salt intake causes a relatively stronger activity of endogenous ET, and that the endogenous ET contributes to the adaptative modulations of sodium excretion via renal tubular action and renin release in association with the changed state of sodium balance.

Chronic blockade of angiotensin II formation during sodium deprivation

1979 ◽  
Vol 237 (6) ◽  
pp. F424-F432 ◽  
Author(s):  
J. E. Hall ◽  
A. C. Guyton ◽  
M. J. Smith ◽  
T. G. Coleman
Keyword(s):  
Renal Function ◽  
Angiotensin Ii ◽  
Marked Decrease ◽  
Enzyme Inhibitor ◽  
Renal Plasma Flow ◽  
Renin Angiotensin System ◽  
Direct Effects ◽  
Filtration Fraction ◽  
Plasma Aldosterone Concentration ◽  
Angiotensin System

The present study was designed to investigate the mechanisms by which the renin-angiotensin system (RAS) regulates arterial pressure (AP) and renal function during chronic sodium deprivation. Intravenous infusion of the converting enzyme inhibitor SQ 14225 (14 microgram.kg-1.mm-1) for 8 days in 12 sodium-deficient dogs caused a marked decrease in AP from 90 +/- 1 to 67 +/- 2 mmHg and a reduction in glomerular filtration rate (GFR), filtration fraction (FF), and plasma aldosterone concentration (PAC). Despite the fall in AP and GFR, urinary Na excretion and effective renal plasma flow (ERPF) increased above control levels. In four dogs, infusion of aldosterone (200 micrograms/day) for 8 days during continuous SQ 14225 infusion restored PAC to levels above control, but did not significantly change AP or renal function from the values observed during SQ 14225 infusion alone. However, infusion of angiotensin II (AII) (10 or 20 ng.kg-1.min-1) for 5––8 days during continuous SQ 14225 infusion almost completely restored AP and renal function to control levels. These data indicate that the RAS plays a major role in regulating AP, renal hemodynamics, and Na excretion during Na deprivation, probably through the direct effects of AII rather than through changes in PAC.

Preoperative Renin-Angiotensin System Inhibitors Protect Renal Function in Aging Patients Undergoing Cardiac Surgery

2011 ◽  
Vol 167 (2) ◽  
pp. e63-e69 ◽  
Author(s):  
Viachaslau Barodka ◽  
Scott Silvestry ◽  
Ning Zhao ◽  
Xiangyin Jiao ◽  
David J. Whellan ◽  
...  
Keyword(s):  
Renal Function ◽  
Cardiac Surgery ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Synergistic Expression of Angiotensin-Converting Enzyme (ACE) and ACE2 in Human Renal Tissue and Confounding Effects of Hypertension on the ACE to ACE2 Ratio

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2453-2457 ◽  
Author(s):  
Shigeyuki Wakahara ◽  
Tadashi Konoshita ◽  
Shinichi Mizuno ◽  
Makoto Motomura ◽  
Chikako Aoyama ◽  
...  
Keyword(s):  
Renal Function ◽  
Angiotensin Converting Enzyme ◽  
Pairwise Comparison ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Converting Enzyme ◽  
Gene Expressions ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Clinicopathological Variables

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.

scholarly journals Effect of Dual Blockade of Renin-Angiotensin System on Proteinuria

2013 ◽  
Vol 1 (1) ◽  
pp. 18-20
Author(s):  
Eqerem Hasani ◽  
Alma Idrizi ◽  
Myftar Barbullushi
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blocker ◽  
Enzyme Inhibitor ◽  
Combined Therapy ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Dual Blockade

Aim: Aim of the study was the evaluation of the effect of dual blockade of the renin-angiotensin system (RAS) on proteinuria. Material and Methods: Sixty patients, included in the study, were treated with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker for a period of 3 months. Results: The dual blockade of RAS resulted with decrease of proteinuria, a slight increase of serum creatinine and was not associated with a lowering of blood pressure.Conclusion: Combined therapy with ACE-I and ARB results in a more complete blockade of the RAS than monotherapy. In proteinuric nephropathies it reduces significantly baseline proteinuria.

Effect of intrarenal renin inhibition on renal hemodynamics and excretory function

1990 ◽  
Vol 259 (1) ◽  
pp. R7-R14 ◽  
Author(s):  
K. M. Verburg ◽  
J. R. Kadam ◽  
G. A. Young ◽  
S. H. Rosenberg ◽  
H. D. Kleinert
Keyword(s):  
Recovery Period ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Electrolyte Excretion ◽  
Angiotensin System ◽  
Excretory Function ◽  
Fractional Excretion Of Sodium ◽  
Renin Inhibition

This study was designed to investigate in sodium-depleted monkeys the renal hemodynamic and excretory effects resulting from blockade of the renin-angiotensin system induced by intrarenal infusion of the primate-selective renin inhibitor A-65317. Intrarenal infusion of A-65317 (n = 6) at a dose of 0.01 micrograms.kg-1.min-1 elicited an increase (P less than 0.05) in renal blood flow (RBF) from 43.5 +/- 2.7 to 49.4 +/- 4.4 ml/min and glomerular filtration rate (GFR) from 6.3 +/- 0.3 to 6.9 +/- 0.4 ml/min, with no significant changes in mean arterial pressure (MAP) or plasma renin activity (PRA). Increases (P less than 0.05) in the urine flow rate (0.18 +/- 0.04 to 0.28 +/- 0.04 ml/min) and the fractional excretion of sodium (0.18 +/- 0.06 to 0.35 +/- 0.13%) were also observed. After a recovery period, the intrarenal infusion dose of A-65317 was increased to 0.1 microgram.kg-1.min-1 and RBF increased (P less than 0.05) from 42.9 +/- 3.9 to 53.0 +/- 3.7 ml/min in conjunction with a significant 85 +/- 4% inhibition of PRA and a 14 +/- 4 mmHg reduction in MAP. GFR and electrolyte excretion remained at control levels. Intrarenal infusion of vehicle (n = 6) had no significant effect on any of the variables studied. In a separate group of monkeys, intravenous (iv) infusion of A-65317 at 0.01 microgram.kg-1.min-1 (n = 5) did not result in significant changes from control.(ABSTRACT TRUNCATED AT 250 WORDS)

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