Effect of the Converting-Enzyme Inhibitor SQ 14 225 (captopril) in Early One-Kidney, One-Clip Hypertension in the Rat

1981 ◽  
Vol 60 (4) ◽  
pp. 387-392 ◽  
Author(s):  
R. Vandongen ◽  
Anne Tunney ◽  
Patricia Martinez
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Enzyme Inhibitor ◽  
Plasma Renin ◽  
Renin Activity ◽  
Converting Enzyme ◽  
Hypotensive Action ◽  
Converting Enzyme Inhibitor ◽  
Restore Blood Pressure ◽  
Arterial Plasma

1. Arterial plasma renin activity was significantly elevated in rats with one-kidney, one-clip hypertension of less than 3 weeks duration. 2. Intraperitoneal injection of the angiotensin-converting enzyme inhibitor SQ 14 225 (captopril) caused a dose-related decrease in systolic blood pressure in hypertensive rats. The lowest dose of captopril used (3.5 mg/kg) inhibited conversion of exogenous angiotensin I and maximally potentiated the depressor response to bradykinin, but failed to restore blood pressure to that of the normotensive controls. 3. Removal of the solitary clipped kidney also did not restore blood pressure to normal. Injection of captopril (3.5 mg/kg) 24 h after nephrectomy, when no circulating renin activity was detectable, lowered blood pressure further in hypertensive but not in similarly nephrectomized controls. 4. These results indicate that raised blood pressure in early one-kidney, one-clip hypertension in the rat cannot be entirely attributed to the renin-angioterisin system, even when plasma renin activity is significantly increased. 5. This study has also confirmed a hypotensive action of captopril in anephric rats when plasma renin activity is undetectable.

Effect of Angiotensin II and Converting Enzyme Inhibitor (Captopril) on Blood Pressure, Plasma Renin Activity and Aldosterone in Primary Aldosteronism

1981 ◽  
Vol 61 (s7) ◽  
pp. 289s-293s ◽  
Author(s):  
F. Mantero ◽  
F. Fallo ◽  
G. Opocher ◽  
D. Armanini ◽  
M. Boscaro ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Primary Aldosteronism ◽  
Enzyme Inhibitor ◽  
Plasma Renin ◽  
Renin Activity ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitor ◽  
Idiopathic Hyperaldosteronism

1. Patients with idiopathic hyperaldosteronism (IHA) show a response of aldosterone to posture which is not present in patients with aldosterone-producing adenoma (APA). We have determined whether this could be explained by a different sensitivity to angiotensin II. 2. Angiotensin II was infused in gradually increasing doses in six patients with APA and in seven patients with IHA. No changes in aldosterone concentration were found at the end of each period in APA, whereas there was a significant increase in IHA; blood pressure rose by a similar extent in both groups. 3. In order to evaluate the role of endogenous angiotensin II, captopril, a converting enzyme inhibitor, was administered to six patients with APA and five patients with IHA at a dose of 75 mg/day for 1 week. There was a significant fall of mean blood pressure in IHA and only minimal changes in APA. Plasma renin activity and plasma and urinary aldosterone were unchanged in APA. In IHA there was a small increase in upright plasma renin activity and a slight decrease in both plasma and urinary aldosterone, but these changes were not significant. 4. These findings further support the idea that idiopathic hyperaldosteronism is a clinical state different from that occurring in primary aldosteronism due to adenoma, and may be more closely related to essential hypertension.

Angiotensin Activates Sympathetic Reflexes in the Anaesthetized Cat

1980 ◽  
Vol 59 (s6) ◽  
pp. 287s-289s ◽  
Author(s):  
D. P. Clough ◽  
R. Hatton ◽  
J. Conway ◽  
S. A. Adigun
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Activity ◽  
Converting Enzyme ◽  
Reduced Pressure ◽  
Converting Enzyme Inhibitor ◽  
Sympathetic Reflexes

1. Lower-body subatmospheric pressure has been used to stimulate sympathetic reflexes in anaesthetized cats and the effects of an angiotensin converting enzyme inhibitor and [Sar1, Ala8]angiotensin II have been investigated on this reflex. 2. At the prevailing level of renin activity (2.9-3.2 ng of angiotensin I h−1 ml−1) the converting enzyme inhibitor had no effect on blood pressure yet it potentiated the initial fall in blood pressure caused by the reduced pressure and it impaired its recovery. After 10 min, therefore, blood pressure was still reduced after converting enzyme inhibitor treatment whereas in control experiments full recovery occurred within 30 s. 3. When converting enzyme inhibitor was given 75 s after the start of a 10 min period of reduced pressure, at a time when plasma renin activity had not been increased, it caused a greater and more sustained fall in pressure than it caused when administered alone. The angiotensin II antagonist, [Sar1,Ala8]angiotensin II, produced similar effects. 4. These findings suggest that the renin-angiotensin system interacts with the sympathetic nervous system to maintain systemic arterial pressure.

Effects of the Oral Angiotensin-Converting Enzyme Inhibitor MK-421 in Human Hypertension

1981 ◽  
Vol 61 (s7) ◽  
pp. 281s-283s ◽  
Author(s):  
H. Gavras ◽  
J. Biollaz ◽  
B. Waeber ◽  
H. R. Brunner ◽  
Gavras Irene ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Plasma Renin Activity ◽  
Enzyme Inhibitor ◽  
Plasma Renin ◽  
Pressure Control ◽  
Renin Activity ◽  
Converting Enzyme ◽  
Blood Pressure Fall ◽  
Plasma Angiotensin

1. The effects of the new oral angiotensin-converting enzyme (ACE) inhibitor MK-421 on blood pressure, plasma renin activity, angiotensin II, aldosterone and converting enzyme activity were assessed in 16 hypertensive patients followed for 6–18 weeks. 2. After an initial titration period, maintenance doses of 2.5–40 mg once daily produced satisfactory blood pressure control in 11 and a partial but significant decrease in the remainder. 3. Treatment was associated with no change in heart rate and no orthostatic hypotension. At 24 h after the first effective dose, blood pressure was still decreased, plasma ACE was suppressed to 16% of the baseline, plasma angiotensin to 58%, aldosterone to 42%, and plasma renin activity was elevated to 228% of the baseline. 4. Magnitude of blood pressure fall was significantly correlated with the height of pretreatment blood pressure but not with baseline levels of plasma renin activity.

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.

Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E2, and kallikrein excretion in conscious rats

1984 ◽  
Vol 62 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Ernesto L. Schiffrin ◽  
Jolanta Gutkowska ◽  
Gaétan Thibault ◽  
Jacques Genest
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Ace Inhibition ◽  
Renin Activity ◽  
Prostaglandin E ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Angiotensin I Converting Enzyme

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunorcactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part β-adrenergically mediated. The negative short feedback loop of angiotensin II and prostaglandins did not appear to be involved. A vasodilator effect, apparently independent of ACE inhibition, was found in intact conscious sodium-replete rats.

Renal Effects of Angiotensin I-Receptor Blockade and Angiotensin Convertase Inhibition in Man

1996 ◽  
Vol 90 (3) ◽  
pp. 205-213 ◽  
Author(s):  
Francois Schmitt ◽  
Svetlozar Natov ◽  
Frank Martinez ◽  
Bernard Lacour ◽  
Thierry P. Hannedouche
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Plasma Renin Activity ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Renin Activity ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibition

1. The objective was to compare two means of inhibition of the renin—angiotensin system [angiotensin-converting enzyme inhibition and selective antagonism of angiotensin II subtype 1 (AT1) receptor] on renal function in 10 healthy normotensive volunteers on a normal sodium diet. Since mechanisms of action may differ between both drugs, a synergistic action was further studied by combining the two drugs. 2. The design was a double-blind randomized acute administration of either placebo or a single oral dose of enalapril, 20 mg, followed in each case by administration of the AT1 selective antagonist losartan potassium, 50 mg orally. 3. The methods included measurements of hormones (plasma renin activity, plasma aldosterone), blood pressure and renal function from 45 to 135 min after administration of placebo or enalapril, and from 45 to 135 min after losartan and placebo or losartan and enalapril. Renal function was studied using clearance of sodium, lithium, uric acid, inulin and para-aminohippuric acid. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was determined and sieving curves were applied on a hydrodynamic model of ultrafiltration. 4. Losartan did not change plasma renin activity, blood pressure or glomerular filtration rate, but increased significantly renal plasma flow and urinary excretion of sodium and uric acid. Enalapril increased plasma renin activity and renal plasma flow, and decreased blood pressure without natriuretic, lithiuretic or uricosuric effects. The renal vasodilatation was potentiated when losartan and enalapril were combined, despite a further rise in plasma renin. In contrast to enalapril, losartan either alone or in combination with enalapril significantly depressed fractional clearances of dextran of small radii (34–42 Å). These changes in fractional clearances of dextran were presumably related to the rise in glomerular plasma flow since the other major determinants of filtration, i.e. transcapillary glomerular pressure gradient, ultrafiltration coefficient and membrane property, were computed as unchanged by either losartan, enalapril or a combination of both. 5. In conclusion, these findings suggest that in normal sodium-repleted man the renal, hormonal and blood pressure effects of AT1 antagonism and angiotensin-converting enzyme inhibition are not strictly similar and could be synergistic.

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