Angiotensin and Renin in Rat and Dog Brain

Abstract

Since the discovery of the angiotensins a link was sought in vain between these polypeptides and the physiological mechanism that regulates the systemic blood pressure (1). This search, however, was rich in surprises as soon as the amazing diversity of pharmacological actions of angiotensin II was established. Besides being the most powerful vasopressor molecule known, the polypeptide is the hormone for aldosterone release (2) and has several effects on the autonomic nervous system: (a) it inhibits the uptake of catecholamines by sympathetic nerve endings (3); (b) it has a direct action on cholinergic ganglionic cells (4); (c) it accelerates the rate of biosynthesis of norepinephrine (5); and (d) it acts directly or indirectly on central sympathetic structures inducing a prolonged increase in blood pressure and heart rate (6). Even if this versatility shattered the early ideas concerning the function of the polypeptide, the classical scheme that accounted for angiotensin I production was not challenged until very recently. The liberation of the polypeptide was supposed to be restricted to the plasma, where a circulating alpha-2 globulin synthetized by the liver, angiotensinogen, is split by a proteolytic enzyme, renin, synthesized by the granular cells of the juxtaglomerular apparatus of the kidney. This proteolytic step releases a 10-residue long polypeptide from angiotensinogen, denominated angiotensin I, which is itself the substrate for a specific, Cl-activated carboxipeptidase, the converting enzyme, giving rise to the octapeptide angiotensin II. This scheme was first questioned after the finding that isolated rat renal glomeruli, devoid of plasma contamination and incubated in a simple salt medium, were able to secrete angiotensin I in great amounts (7-8). The release of the polypeptide was suppressed with protein-synthesis inhibitors. I The tissue synthesis of angiotensin I was strongly supported by the finding of a polypeptide in several tissues of the rat and the dog with pharmacological and

Effects of Angiotensin Ii on the Medullaryneurons and Their Sensitivity to Acetylcholine and Catecholamines

“…On the other hand, Hoffman and Phillips (18) reported that the most sensitive site of the hyper tensive effect of AT,, was the ventral anterior third ventricle or perivascular tissue sur rounding it and that the hypertensive effect was not apparent when AT,, was applied to the fourth ventricle. Although it has been reported that renin and angiotensin are endogenous (19,20) and that angiotensin in the dog brain is concentrated in the brainstem (19), this octapeptide is apparently not directly concerned with central vasomotor control mechanisms in the medulla, as in experiment, AT,, sensitive neurons showed no characteristic localization.…”

Differential effect of angiotensin II and blood pressure on hippocampal inflammation in mice

“…The brain also has its own intrinsic reninangiotensin system from where Ang II is produced [25][26][27][28]. In rodents and humans, Ang II binding sites are expressed widely throughout the brain including the cerebral vasculature and circumventricular organs (CVO), where they have access to systemic Ang II [27,29,30].…”

Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system

“…[1][2][3] By contrast, much less is known about the tissue RAS, and many questions about the angiotensin processing cascade and the role of the tissue RAS in regulating blood pressure and fluid balance remain unanswered. [4][5][6][7] Proangiotensin-12 (proang-12) is a 12-amino acid, C-terminal extended form of Ang I, which we recently isolated from rat small intestine. 8 In vitro, proang-12 constricts aortic strips and, when intravenously infused into rats, raises blood pressure.…”