Response of Mineralocorticoid Hypertensive Animals to an Angiotensin I Converting Enzyme Inhibitor

Douglas, Ben H.; Langford, Herbert G.; McCaa, Robert E.

doi:10.3181/00379727-161-40496

Cited by 30 publications

(9 citation statements)

References 4 publications

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“…8 Furthermore, chronic captopril infusion has no effect on either arterial pressure or renal function in circumstances in which endogenous Ang II formation is suppressed to undetectable levels, as occurs with high sodium intake, deoxycorticosterone acetate hypertension, or chronic Ang II hypertension. 34 ' 35 Therefore, the present findings and the results from other chronic studies support the contention that the major effects of captopril on renal function in the present study were mediated via blockade of Ang II formation.…”

supporting

confidence: 80%

Preservation of renal function by angiotensin during chronic adrenergic stimulation.

Lohmeier

Yang

1991

Hypertension

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The purpose of the present study was to determine the role of angiotensin II (Ang II) in mediating renal responses to chronic intrarenal norepinephrine infusion. Norepinephrine was continuously infused for 5 days into the renal artery of unilaterally nephrectomized dogs at progressively higher daily infusion rates: 0.05, 0.10, 0.20, 030, and 0.40 /tg/kg/min. In three additional groups of dogs, norepinephrine infusion was repeated during chronic intravenous captopril administration to fix plasma Ang II concentration at 1) low levels (no Ang II infused), 2) high levels in the renal circulation (Ang II infused intrarenally at a rate of 1 ng/kg/min), and 3) high levels in the systemic circulation (Ang II infused intravenously at a rate of 5 ng/kg/min). In the control group of animals with intact renin-angiotensin systems, there were progressive increments in mean arterial pressure (from 96±4 to 141±6 mm Hg) and plasma renin activity (from 0.4±0.1 to 10.9 ±4.5 ng angiotensin I/ml/hr) and concomitant reductions in glomerular filtration rate and renal plasma flow to approximately 40% of control during the 5-day norepinephrine infusion period. In marked contrast, when captopril was infused chronically without Ang II, mean arterial pressure was 20-25 mm Hg less than that under control conditions, and the renal hemodynamic effects of norepinephrine were greatly exaggerated; by day 3 of norepinephrine infusion, both glomerular filtration rate (16±2% of control) and renal plasma flow (12±4% of control) were considerably lower than values in control animals (86±4% and 80±8% of control, respectively). Similarly, when a high level of Ang II was localized in the renal circulation during captopril administration, mean arterial pressure was depressed, and again there were pronounced renal responses to norepinephrine. Conversely, when Ang II was infused intravenously during captopril administration, mean arterial pressure was not reduced, and the glomerular filtration rate and renal plasma flow responses to norepinephrine were similar to those that occurred under control conditions. These findings indicate that the renin-angiotensin system prevents exaggerated renal vascular responses to chronic norepinephrine stimulation by preserving renal perfusion pressure. (Hypertension 1991;17:278-287)

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supporting

confidence: 80%

Preservation of renal function by angiotensin during chronic adrenergic stimulation.

Lohmeier

Yang

1991

Hypertension

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“…Reports of the effect of captopril on blood pressure in DOC-salt hypertensive rats area conflicting. 23 ' 24 In the present study, captopril had no effect on blood pressure in DOC-salt hypertensive rats, even though the arterial plasma level of kinins was increased relative to the values in hypertensive rats without captopril treatment. Concerning this point, it has been reported that blood pressure does not fall in intact rats receiving bradykinin infusion until the arterial blood kinin concentration greatly exceeds the basal kinin level.…”

Section: Discussioncontrasting

confidence: 57%

Plasma kinin concentration in deoxycorticosterone-salt hypertension.

Nakagawa

Nasjletti

1988

Hypertension

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SUMMARY We investigated the status of circulating kinins in rats with severe hypertension caused by drinking 1% NaCl (saline) and treatment with deoxycorticosterone (DOC, 25 mg/kg/wk s.c.) for 5 weeks. Saline-drinking rats treated with DOC had a higher systolic blood pressure (210 ± 4 mm Hg) than did rats without DOC treatment drinking water (138 ± 3 mm Hg) or saline (141 ± 3 nun Hg). The concentration of kinins in the inferior vena cava plasma of DOC-salt hypertensive rats did not differ from the venous plasma kinin concentration in normotensive rats drinking water or saline. In contrast, the arterial plasma kinin concentration in DOC-salt hypertensive rats (7.0 ± 0.8 pg/ml) was lower ( p < 0.002) than that in water-drinking controls (14.0 ± 2.2 pg/ml); it also was lower (p<0.005) in saline-drinking rats (8.1 ± 0.9 pg/ml) than in water-drinking controls. Infusion of bradyklnin (20 /ig/kg/min i.v.) increased arterial plasma kinins in all the groups. Nonetheless, the arterial plasma kinin concentration achieved during brad> kinin infusion in DOC-salt hypertensive (1590 ± 130 pg/ml) and in saline-drinking rats (1540 ± 100 pg/ml) was lower than that in water-drinking rats (2140 ± 210 pg/ml). On the other hand, during infusion of the kininase II inhibitor captopril (80 /xg/hr i.p.) for 3 days, neither DOC-salt hypertensive rats nor saline-drinking normotensive rats exhibited significant reduction of arterial plasma kinins relative to the level in water-drinking controls. These data indicate that high salt intake, irrespective of the level of blood pressure, causes the arterial plasma concentration of kinins to fall. The observed reduction of arterial plasma kinins in DOC-salt hypertensive rats and in saline-drinking normotensive rats may be the expression of increased kinin degradation. (Hypertension 11: 411-415, 1988 Received August 27, 1987; accepted November 18, 1987. development of hypertension remains unknown. Kinins occur in circulating blood at concentrations that reflect the balance between kinin generation by kallikreins and kinin inactivation by kininases. 3 The status and importance of blood kinins in relation to the development of hypertension are also unknown. 6 ' 7 According to a recent report, 8 the arterial blood concentration of kinins in rats with severe one-kidney, one clip hypertension is increased. Severe hypertension causes vascular injury and, consequently, may create a setting that favors activation of plasma prekallikrein and augmentation of blood kinin generation and levels.9 If so, severe hypertension, regardless of its cause, may be expected to increase circulating kinins. This report details the results of experiments aimed at contrasting the concentration of kinins in the plasma of normotensive rats and of rats with severe hypertension caused by treatment with deoxycorticosterone (DOC) and increased dietary sodium.

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“…SBP, heart rate, and body weight were measured 3 days before drug treatment was begun and at weeks 2,4,6,8,12, and 20 during drug administration. The water intake was estimated at week 16 during drug administration.…”

Section: Drug Treatment Regimen and Measurement Of Blood Pressurementioning

confidence: 99%

“…20 Endothelial cells were removed by rubbing the inner surface of aortic tissue with a cotton stick for 1 minute. The aortic strip was suspended in an organ bath containing 30 ml KHS maintained at 36.5±0.5° C and aerated with a 5% CO 2 Isometric tension of the aorta was measured with a force-displacement transducer (TB-612T, Nihonkohden, Tokyo, Japan) connected to a carrier amplifier (AP-601G, Nihonkohden) and was recorded on a thermal-pen-writing recorder (RJG-4128, Nihonkohden).…”

Section: Experimental Protocol With the Isolated Aortamentioning

confidence: 99%

Long-term inhibition of angiotensin converting enzyme suppresses calcium channel agonist-induced contraction of aorta in hypertensive rats.

1989

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To elucidate functional changes in the vascular smooth muscle of spontaneously hypertensive rats (SHR) after chronic inhibition of angiotensin converting enzyme, we examined the contractile responses to different pharmacological interventions in the isolated aortas from SHR treated with a novel angiotensin converting enzyme inhibitor, CS-622 (10 mg/kg/day) for 20 weeks. In normal K + medium, a marked contraction was elicited by increasing Ca 2+concentration from 0 to 3 mM in aortas from a control group of SHR, but not in aortas from SHR treated with CS-622. In 60 mM K + medium, however, the sensitivity of aorta to Ca 2+ was almost the same in the two groups. A calcium channel activator, CGP-28392 (10~7 to 10"' M), induced a marked contraction in the aortas from control SHR, but not in the aortas from CS-622-treated SHR. When slightly depolarized in 10 or 12 mM K + solution, the aortas from CS-622-treated SHR contracted in response to CGP-28392. The aortic sensitivity to KC1 contraction was much lower in CS-622-treated SHR than in untreated SHR, whereas the sensitivity to phenylephrine contraction was little different in the two groups. These contractile profiles of aortas from CS-622-treated SHR were very similar to those from normotensive Wistar-Kyoto rats but not to those from hydralazine-treated SHR. These data suggest that contractions due to Ca 2+ through voltage-dependent calcium channels are exaggerated in SHR aorta and that long-term treatment with angiotensin converting enzyme inhibitor suppresses the abnormal contractility of SHR vascular smooth muscle, probably through alterations of voltage-related functions of calcium channels. (Hypertension, 1989;14:652-659) A ntihypertensive effects of acute inhibition of angiotensin converting enzyme (ACE) depend on the status of the renin-angiotensin system: acute ACE inhibition produces a marked hypotension in renovascular hypertensive rats and a moderate hypotension in spontaneously hypertensive rats (SHR), whereas it is totally ineffective in reducing blood pressure of deoxycorticosterone acetate-salt hypertensive rats. 1 * 2 However, chronic ACE inhibition has been shown to lower blood pressure of SHR to levels of normotensive Wistar-Kyoto (WKY) rats, which is never accomplished by acute inhibition of ACE.3 These facts suggest that antihypertensive mechanisms underlying chronic ACE inhibition differ from those of acute ACE inhibition. Angiotensin II From the Cardiovascular Division, Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.Address for reprints: Hiroyuki Koike, PhD, Biological Research Laboratories, Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawaku, Tokyo 140, Japan.Received January 31, 1989; accepted in revised form Jury 24, 1989. (Ang II), when infused chronically at a dose below the threshold of the acute pressor effect, does not increase blood pressure initially, but increases blood pressure gradually over several days.4 -6 Thus, Ang II has a slow pressor action that is different from its acute pressor action. A recent report...

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Response of Mineralocorticoid Hypertensive Animals to an Angiotensin I Converting Enzyme Inhibitor

Cited by 30 publications

References 4 publications

Preservation of renal function by angiotensin during chronic adrenergic stimulation.

Preservation of renal function by angiotensin during chronic adrenergic stimulation.

Plasma kinin concentration in deoxycorticosterone-salt hypertension.

Long-term inhibition of angiotensin converting enzyme suppresses calcium channel agonist-induced contraction of aorta in hypertensive rats.

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