Search

Five patients with chronic pulmonary diseases (3 pulmonary emphysema, 1 chronic respiratory failure caused by old tuberculosis, 1 diffuse panbronchiolitis) showed a marked increase of plasma angiotensin-I and PRA level, which was accompanied by an increase of angiotensin-II level, however, whose systemic blood pressure was not elevated. The intravenous infusion of angiotensin-II-analogue (1-Sarcosine, 8-Isoleucine-Angiotensin-II) elicited an antagonistic blood pressure response resembling Bartter's syndrome.

The purpose of this study was to compare the acute hypotensive efficacy of different types of inhibitor of the renin-angiotensin system. A renin inhibitor (RI), CGP 44,099 A, a converting enzyme inhibitor (CEI), enalaprilat, a peptidic angiotensin II (Ang II) antagonist, [Sar1, Ile8]Ang II (P-Ang IIA), and a nonpeptidic Ang II antagonist devoid of agonistic properties, 2-butyl-4-chloro-1- ([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)-5- (hydroxymethyl)imidazol (NP-Ang IIA), were administered intravenously to sodium-depleted rats (SDRs), renal hypertensive rats (two-kidney, one-clip) (RHRs), and spontaneously hypertensive rats (SHRs). The four compounds were all effective in lowering blood pressure (BP) in SDRs and RHRs. The maximum hypotensive response observed within 30 min of administration was similar for all four compounds (approximately 30 mm Hg in SDRs and 60 mm Hg in RHRs). In SHRs, the P-Ang IIA induced a pressor response whereas the RI, CEI, and NP-Ang IIA lowered BP to a similar extent (approximately 15 mm Hg). Pretreatment with the CEI completely prevented the hypotensive response to RI in SHRs, and vice versa. These observations indicate that the principal mechanism by which converting enzyme inhibitors lower BP after acute administration in these rat models is by inhibition of the formation of Ang II. The pressor response to the P-Ang IIA in SHRs is probably a consequence of its partial agonistic properties. Renin inhibitors and nonpeptidic Ang II antagonists, devoid of agonistic properties, promise to be effective antihypertensive agents similar to the CEIs.

1 The mechanism involved in catecholamine (CA) release from the cat adrenal gland in response to insulin hypoglycaemia was studied. In intact cats, hypoglycaemia induced an 11 fold increase in adrenomedullary CA secretion. 2 Acute bilateral nephrectomy nearly abolished the increased CA release from the adrenal gland during hypoglycaemia. 3 Infusion of Sar1-Ileu8-Angiotensin II (AII), a competitive AII antagonist, suppressed the adrenomedullary response to the insulin-induced hypoglycaemia. After termination of the antagonist infusion CA secretion from the adrenal medulla increased rapidly, reaching the same level as in insulin-treated cats. 4 Infusion of rabbit anti-angiotensin I antibodies suppressed CA release from the adrenal gland of hypoglycaemic cats. This effect was more prolonged than that of Sar1-Ileu8-AII. 5 These results indicate that CA release from the adrenal medulla of the cat in response to insulin-induced hypoglycaemia, is mediated through the renal reninangiotensin system. Since hypoglycaemia causes sympathetic stimulation through a central mechanism, angiotensin may act through the central nervous system.

In order to evaluate the role of the renin-angiotensin system and the sympathetic nervous system in the maintenance of blood pressure in the sodium-depleted state, the changes of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and plasma noradrenaline (PNA) were examined in unanesthetized dogs after the administration of furosemide. Furthermore, the role of the renin-angiotensin system in the increased sympathetic nerve activity induced by furosemide was assessed by using Sar1-Ile8-angiotensin II, an angiotensin II antagonist. When a dose of 0.8 mg/kg of furosemide was injected intravenously, 3 times every 15 minutes, PRA and PNA were significantly increased with a concomitant increase in PAC. Sar1-Ile8-angiotensin II induced a significant increase in PAC and a slight increase in PRA, while no changes were found in PNA and the mean blood pressure. The increase in PNA induced by furosemide was inhibited dose-dependently by Sar1-Ile8-angiotensin II, through PRA and PAC were further increased. There results suggest that an administration of furosemide induced the increase in PNA and the increase in PNA by furosemide might by mediated by the renin-angiotensin system.

The role of the renin-angiotensin system in the development of hypertension was studied by infusing an angiotensin II analog, 1-Sar, 8-Ile angiotensin II, in women with toxemia and women on estrogen-containing oral contraceptives or estrogen treatment. In 3 of 4 women who developed hypertension on oral contraceptives or estrogen treatment, the blood pressure was reduced with the infusion of 1-Sar, 8-Ile angiotensin II. In 3 women who remained normotensive on oral contraceptives or estrogen treatment, the blood pressure was not reduced, although there was no significant difference in plasma renin activity (PRA) between the women who developed hypertension and those who remained normotensive on oral contraceptives. In 6 pregnant women who developed hypertension, the blood pressure increased remarkably with the infusion of 1-Sar, 8-Ile angiotensin II, although PRA was increased significantly in all of them. In these women, however, sodium excretion was less than that in normal pregnant women. In 4 normal pregnant women, the blood pressure remained unchanged or increased slightly, and PRA was almost similar to that of women who developed hypertension. The above results suggest that increased PRA in women who developed hypertension whilst on estrogen-containing oral contraceptives or estrogen treatment is more closely related to the development or maintenance of hypertension than that in pregnant women who develop hypertension, although there remains a possibility that the response of blood pressure to 1-Sar, 8-Ile angiotensin II in pregnant women who develop hypertension is influenced by sodium retention.

Isoproterenol infusion (0.1 microgram/kg per min) into the renal artery of the cat induced an increase in plasma renin concentration (PRC) from 14.3 +/- 5.7 (mean +/- SE) ng angiotensin I/ml per hr to 56.8 +/- 7.7 after 70 minutes (P < 0.05) and an increase in catecholamine secretion rate from 38.7 +/- 6.0 ng/kg per 10 min to 180.0 +/- 40.0 after 70 minutes (P < 0.001). Intravenous infusion of the same dose of isoproterenol had no significant effect on adrenomedullary catecholamine secretion rate. Isoproterenol induced preferential norepinephrine release: the ratio of norepinephrine to epinephrine secretion changed from 11.5:23.7 during the control period to 130.0:40.1 70 minutes after the start of isoproterenol administration. Intrarenal infusion of propranolol (3.0 mg/kg per min) inhibited renal renin release and adrenal catecholamine secretion in response to intrarenal isoproterenol. Intravenous infusion (0.4 microgram/kg per min) of an angiotensin II antagonist [Sar1, Ileu8]angiotensin II abolished the catecholamine response to intrarenal isoproterenol infusion. It is suggested that intrarenal isoproterenol infusion stimulates renal renin release and angiotensin production which, in turn, stimulates a preferential secretion of adrenomedullary norepinephrine.

Prehypertensive rabbits with renal artery stenosis of 3 days' duration (one-kidney, one clip) are known to have increased pressor responses to norepinephrine and vasopressin; this pressor hyperresponsiveness is restored to normal by the angiotensin II (AII) antagonist, [ Sar1, Ile8 ] AII, even though plasma renin activity (PRA) and plasma AII concentrations are not elevated. In the present study, the cross-circulation of blood between conscious one-kidney, 3-day renal artery stenosis rabbits and conscious normal rabbits resulted in the transfer of pressor hyperresponsiveness to the normal rabbits, although both groups of rabbits had normal values for PRA. A similar cross-circulation of blood between one-kidney rabbits without renal artery stenosis and normal rabbits did not alter the pressor responsiveness of the normal rabbits to norepinephrine. It was concluded that a circulating humoral factor is involved in mediating pressor hyperresponsiveness in 3-day renal artery stenosis rabbits. To evaluate the interrelationship between AII and the hormonal hyperresponsiveness factor, an additional experiment was performed in which blood was cross-circulated between one-kidney, 3-day renal artery stenosis rabbits and normal rabbits, with the normal rabbits receiving [ Sar1, Ile8 ] AII immediately following cross-circulation. Administration of this AII antagonist to the normal rabbits prevented them from showing pressor hyperresponsiveness following the cross-circulation of blood. It is concluded that in this prehypertensive renal artery stenosis model the humoral hyperresponsiveness factor exerts its effect through AII mechanisms, rather than AII acting to increase the release or secretion of the hyperresponsiveness factor.

Many avian species demonstrate atherosclerosis and high blood pressure (BP) that are influenced by age, sex, diet, and environment, but show no arteriosclerosis in small vessels. Thus, we aimed to define neural and humoral control of BP in conscious, 32-wk-old female chickens, Gallus gallus. Mean aortic pressure (determined by chronically implanted catheter) was 137.6 +/- 2.0 mm Hg; heart rate was 295 +/- 4 beats/min. Plasma renin activity (PRA), measured by radioimmunoassay of fowl angiotensin I ([Asp1, Val5, Ser9]AI), and plasma angiotensinogen levels were 3.55 +/- 0.31 ng/ml/hr and 1229 +/- 66 ng/ml respectively. Repeated injection of propranolol (4 to 8 mg/kg/day, i.m.) decreased (p less than 0.01) the BP 19.1 +/- 3.0 mm Hg and heart rate 76 +/- 6 beats/min. Acute infusion of propranolol also markedly reduced BP and heart rate, and increased plasma levels of norepinephrine and epinephrine. SQ 14,225 (20 mg/kg/day) reduced BP (p less than 0.01), but BP returned towards original levels unless a higher dose was given. PRA increased 2- to 6-fold. BP also decreased 31.0 +/- 2.1 mm Hg after reserpine treatment, but not after [Sar1, Ile8]AII. These results suggest that in maintaining BP in fowl the beta-adrenergic function is important, whereas the renin-angiotensin system may not have a primary role.

The cardiovascular responses to intracerebroventricular (i.c.v.) injection of renin were compared between freely moving normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The i.c.v. injection of renin (0.05-1.0 mU) produced a dose-dependent and a long-lasting rise in mean blood pressure associated with variable changes in heart rate (HR) in both WKY and SHR. However, the blood pressure and HR were not affected by intravenously injected renin (0.1 mU). The pressor response to i.c.v. injected renin was greater in SHR than in WKY, the dose-response curve for renin in SHR being to the left of that in WKY. Central (i.c.v.) pretreatment with [Sar1, Ile8]angiotensin II (50 micrograms) largely abolished the pressor response to i.c.v. injected renin in both WKY and SHR. The i.c.v. injection of angiotensin II (ANG II) (10-100 ng) induced a dose-dependent pressor response which was antagonized by central pretreatment with [Sar1, Ile8]ANG II (50 micrograms). The pressor response to ANG II was also greater in SHR than in WKY. These results suggest that the pressor response to centrally administered renin as well as to ANG II, which is mediated via ANG II receptors located in the brain, is enhanced in SHR.