Effects of converting-enzyme inhibitor on hemodynamic actions of ANP in renal hypertensive rats

1989 ◽  
Vol 257 (2) ◽  
pp. R365-R369
Author(s):  
M. G. Salom ◽  
F. J. Fenoy ◽  
A. C. Ingles ◽  
L. Martinez ◽  
T. Quesada
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitor ◽  
Peripheral Resistance ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Hemodynamic Effects ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Induced Hypotension ◽  
Renal Hypertensive Rats

In the present study, we have evaluated whether the hemodynamic effects of atrial natriuretic peptide (ANP) infusion in two-kidney, one-clip (2K, 1C) hypertensive rats are mediated by inhibition of the renin-angiotensin system (RAS). Hemodynamic determinations were performed by thermodilution in conscious, chronically instrumented animals. ANP (1.5 micrograms.kg-1.min-1) and converting-enzyme (CE) inhibitor captopril (1 mg/kg plus 1 mg.kg-1.h-1), produced a similar fall of blood pressure through different hemodynamic mechanisms. ANP induced hypotension by decreasing cardiac index (CI; from 337.3 +/- 24.9 to 255.1 +/- 21.3 ml.min-1.kg-1, P less than 0.001), whereas a fall in total peripheral resistance (TPR) was observed during CE inhibition (from 0.568 +/- 0.02 to 0.488 +/- 0.02 mmHg.min.ml-1.kg, P less than 0.05). In addition, the ANP-induced decrease in CI was not significantly modified by previous CE inhibition. Furthermore, the decrease in TPR induced by CE inhibition did not change when CE inhibitor was administered during ANP treatment. The results of the present study indicate that the acute hemodynamic responses to ANP in 2K, 1C hypertensive rats are not mediated through antagonism of the vasoconstrictor actions of the RAS.

Blood Pressure Response of Nephrectomized Hypertensive Rats to Converting Enzyme Inhibition: Evidence for Persistent Vascular Renin Activity

1977 ◽  
Vol 52 (3) ◽  
pp. 299-304 ◽  
Author(s):  
H. Thurston ◽  
J. D. Swales
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Activity ◽  
Converting Enzyme ◽  
Bilateral Nephrectomy ◽  
Hypertensive Rats ◽  
Angiotensin System

1. Blood pressure and plasma renin activity were studied after bilateral nephrectomy in groups of rats with hypertension caused by unilateral renal ischaemia with the opposite kidney left intact. 2. Although blood pressure showed only a small fall in the first hour after bilateral nephrectomy, plasma renin activity fell rapidly with a half-life of 10 min. 3. Infusion of converting enzyme inhibitor (SQ20881) produced a 26·1% fall in blood pressure 1 h after nephrectomy, 24·0% at 2 h and 4·6% at 6 h. 4. An angiotensin antagonist (Sar1-Ala8-angiotensin II) was infused into hypertensive rats 1 h after nephrectomy; this blocked the vasodepressor action of the converting enzyme inhibitor, indicating that the fall in blood pressure produced by the inhibitor was due to its action upon the renin-angiotensin system. 5. The renin—angiotensin system maintains blood pressure in this model even after plasma renin has fallen to insignificant levels. This supports the view that vascular renin activity has a longer half-life than circulating renin and is important in the control of blood pressure.

Response of Chronic Renovascular Hypertension to Surgical Correction or Prolonged Blockade of the Renin–Angiotensin System by Two Inhibitors in the Rat

1980 ◽  
Vol 58 (1) ◽  
pp. 15-20 ◽  
Author(s):  
H. Thurston ◽  
R. F. Bing ◽  
E. S. Marks ◽  
J. D. Swales
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitor ◽  
Blood Pressure Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Chronic Hypertension ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Converting Enzyme Inhibitor

1. Removal of the renal artery constriction but not of the clipped kidney restored the blood pressure to normal levels in Goldblatt two-kidney rats with hypertension of more than 4 months' duration. 2. Despite the differences in blood pressure response, both surgical procedures lowered plasma renin concentration to normal or below normal values. 3. Administration of the oral converting enzyme inhibitor SQ 14 225 produced a marked fall in blood pressure in Goldblatt kidney rats with chronic hypertension. However, a prolonged infusion of the angiotensin II antagonist saralasin was quite ineffective. The difference in response to the two inhibitors may have been due to bradykinin potentiation by the converting enzyme inhibitor. 4. Although plasma renin is often elevated in Goldblatt two-kidney rats with hypertension of more than 4 months' duration, the renin-angiotensin system plays no role in the maintenance of blood pressure at this stage.

Vasodepressor Property of the Converting Enzyme Inhibitor Captopril (SQ 14 225): The Role of Factors other than Renin-Angiotensin Blockade in the Rat

1980 ◽  
Vol 58 (1) ◽  
pp. 1-6 ◽  
Author(s):  
E. S. Marks ◽  
R. F. Bing ◽  
H. Thurston ◽  
J. D. Swales
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Converting Enzyme Inhibitor ◽  
Blood Pressure Fall ◽  
Angiotensin Blockade ◽  
Pressure Fall

1. The peptide converting enzyme inhibitor captopril was given (1·25 mg/kg intravenously) to normal and nephrectomized rats and rats with renovascular and deoxycorticosterone hypertension. 2. Captopril lowered blood pressure to a small extent in normal and nephrectomized rats. Bradykinin infusion in nephrectomized animals, however, potentiated the vasodepressor action of captopril. 3. Captopril produced a major blood pressure fall in the early stages of Goldblatt two-kidney one-clip hypertension: even when hypertension had been present for more than 4 months, a substantial vasodepressor action was seen. Rats with deoxycorticosterone-induced hypertension also showed a significant blood pressure fall. 4. Captopril was given to salt-loaded and salt-depleted rats in which the renin-angiotensin system had been blocked by infusion of the competitive angiotensin II antagonist saralasin. Captopril still lowered blood pressure in the salt-depleted group. 5. Captopril lowers blood pressure in situations where the renin-angiotensin system is not responsible for blood pressure maintenance. Further, the fall in blood pressure produced in Goldblatt two-kidney one-clip hypertension is greater than would be predicted on the basis of renin-angiotensin blockade. It is likely therefore that captopril lowers blood pressure by an action additional to angiotensin blockade. Bradykinin potentiation is one possible mechanism by which this may take place.

AHU377+Valsartan (LCZ696) Modulates Renin–Angiotensin System (RAS) in the Cardiac of Female Spontaneously Hypertensive Rats Compared With Valsartan

2019 ◽  
Vol 24 (5) ◽  
pp. 450-459 ◽  
Author(s):  
Yang Zhao ◽  
Ruixin Ma ◽  
Xiaorong Yu ◽  
Ningyin Li ◽  
Xu Zhao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mrna Expression ◽  
Spontaneously Hypertensive Rats ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Oxide Synthase

Background: Hypertension is a major cause of death and morbidity worldwide and is increasing in prevalence. The Renin–angiotensin system (RAS) is the most common mechanism involved in the pathophysiology of hypertension. Understanding the mechanism of the pathophysiologic processes will help direct potential therapeutic strategies to treat hypertension and improve cardiac function. Recently, a novel drug LCZ696 containing both an angiotensin receptor blocker valsartan and a neprilysin inhibitor (AHU377) has shown a promising effect on the treatment of hypertension. However, the effects of LCZ696 on the expression of main components of RAS, namely, angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1 R), angiotensin II type 2 receptor (AT2 R), and angiotensin (1-7) receptor/Mas receptor (MasR) remain unclear. The aim of the present study was to evaluate the effects of LCZ696 on the protective arms of RAS in the cardiac tissue when compared with valsartan under the equal inhibition of AT1 R. We hypothesized that the superior effects of LCZ696 may contribute to its greater effect on the RAS than valsartan. Materials and Methods: Sixteen-week-old female spontaneously hypertensive rats (SHRs) were used in this study. Wistar-Kyoto (WKY) rats were used as controls. All rats were randomly divided into LCZ696 (n = 10), valsartan (n = 10), SHR (n = 10), and WKY (n = 10) groups under a 12-hour dark and 12-hour light cycle and provided with regular chow diet and water. The tail-cuff method was performed to measure blood pressure. Cardiac function was assessed by echocardiography. Results: The blood pressure value was lower in LCZ696 than valsartan in SHR after 12 weeks of treatment. Further, LCZ696 inhibits the ACE and AT1 R protein expression in the cardiac of SHR and significantly upregulate the protective axis of RAS components, including ACE2, MasR, and AT2 R. Left ventricular AT2 R messenger RNA (mRNA) expression was higher in the LCZ696+SHR group compared with valsartan. In addition, real-time polymerase chain reaction analysis revealed that LCZ696 enhanced the mRNA expression of antihypertensive components AT2 R, ACE2, and MasR and decreased the expression of AT1 R. However, only AT2 R and ACE2 mRNA expressions have a statistical difference between the LCZ696 and valsartan groups. No difference was observed in the mRNA expression of ACE and MasR. The stronger positive signal of transforming growth factor β in the left ventricle was inhibited in each administrated group compared with SHR groups. Conclusions: LCZ696 ameliorates the vasoconstrictor axis of the RAS AT1 R and stimulate the protective arm effectors, ACE2 and AT2 R, as well as reverses the compensatory upregulation of neuronal nitric oxide synthase and endothelial nitric oxide synthase in SHR. These findings suggest the mechanistic insight of the cardiac-protective and greater hypotensive effects of LCZ696.

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