Pathways of angiotensin formation and function in the brain.

Abstract

New findings from this laboratory suggest that fragments of angiotensin derived from the amino (N-)terminus are biologically active end products of the renin-angiotensin system. In vitro and in vivo experiments revealed that the heptapeptide angiotensin-(l-7) [Ang-(l-7)] is a major endogenous product of the renin-angiotensin system cascade in the brains of rats and dogs. Additional studies with enzyme inhibitors showed that Ang-(1-7) is produced directly from angiotensin I by an enzyme other than the angiotensin converting enzyme. Immunocytochemical analysis revealed the presence of specific staining for immunoreactive Ang-(l-7) in neurons and fibers within the hypothalamo-neurohypophyseal vasopressinergic system of the rat. Although Ang-(l-7) is as potent as angiotensin II (Ang II) in stimulating release of vasopressin from superperfused hypothalamo-neurohypophyseal explants, the heptapeptide has no dipsogenic or vasoconstrictor activity. In contrast, Ang-(1-7) mimics the effects of Ang II in augmenting the intrinsic discharge rate of neurons within the vagal-solitary complex and in causing monophasic depressor responses after microlnjection into the medial region of the nucleus tractus solitarii. The evidence obtained in these experiments suggests novel mechanisms for the generation of angiotensin peptides in the brain. Additionally, the findings suggest that some of the biological actions ascribed to Ang II might be conveyed by the endogenous production of other angiotensin peptides that are generated by enzymatic pathways alternate to those described in the peripheral circulation. (Hypertension 1990;15(suppl I):I-13-I-19)

The role of bradykinin, AT2 and angiotensin 1–7 receptors in the EDRF‐dependent vasodilator effect of angiotensin II on the isolated mesenteric vascular bed of the rat

“…Ang II could be transformed into Ang 1-7 by carboxypeptidase P, or might also stimulate the Ang 1-7 receptor (Ferrario et al, 1990). Our study demonstrates that Ang 1-7 induces a significant vasodilator effect on the MVB in the same dose range of Ang II.…”

Effect of selective angiotensin antagonists on the antidiuresis produced by angiotensin-(1-7) in water-loaded rats

“…Blockade of the antidiuretic effect of Ang- (1)(2)(3)(4)(5)(6)(7). As shown in Figure 1, Losartan completely blocked the antidiuretic effect of Ang-(1-7) in water-loaded rats.…”

“…The heptapeptide angiotensin-(1-7) (Ang-(1-7)) is a recently identified active component of the renin-angiotensin system that can be formed by a route independent of angiotensin converting enzyme (1)(2)(3). Ang- (1)(2)(3)(4)(5)(6)(7) has been demonstrated in plasma and tissues of a variety of species, including man, dogs, sheep and rats (3)(4)(5).…”

“…Ang- (1)(2)(3)(4)(5)(6)(7) has been demonstrated in plasma and tissues of a variety of species, including man, dogs, sheep and rats (3)(4)(5).…”

Renal actions of angiotensin-(1-7)

“…As documented above, in the past few years a large body of evidence has been accumulated suggesting a role for Ang- (1)(2)(3)(4)(5)(6)(7) in the control of hydroelectrolyte balance. However, due to several factors discussed below there is no consensus regarding the major action of Ang-(1-7) in the kidney.…”