Ang IV (ang + iv)

Distribution by Scientific Domains

Selected Abstracts

In vivo characterization of the angiotensin-(1,7)-induced dopamine and ,-aminobutyric acid release in the striatum of the rat

Bart Stragier
Abstract The effect of angiotensin (Ang)-1,7 on dopamine, ,-aminobutyric acid (GABA) and glutamate release in the striatum of the rat was examined using in vivo microdialysis. Ang-(1,7) was administered locally in the striatum through the microdialysis probe. At a concentration of 100 Ám, Ang-(1,7) caused a significant increase in extracellular dopamine and GABA but had no effect on glutamate release. The Ang-(1,7)-induced dopamine release was blocked by EC33, an inhibitor of aminopeptidase A, an enzyme which converts Ang-(1,7) into Ang-(3,7), suggesting that this effect occurs after metabolism into Ang-(3,7). Indeed, administration of Ang-(3,7) (10,100 Ám) into the striatum caused a more potent increase in the striatal dopamine release than Ang-(1,7). Because Ang-(3,7) is an inhibitor of insulin-regulated aminopeptidase (IRAP) and because Ang IV, another IRAP inhibitor, also causes a concentration-dependent increase in dopamine in the rat striatum, IRAP may be involved in this effect. In contrast, EC33 had no effect on the Ang-(1,7)-induced GABA increase but the GABA release was blocked by the putative AT1-7 receptor antagonist A779 (0.1 Ám) and by the nitric oxide synthase inhibitor L-NAME (1 mm). These drugs could not block the effect of Ang-(1,7) on the striatal dopamine release suggesting that only the observed effects on GABA release are mediated by the AT1-7 receptor and/or are associated with a release of nitric oxide. [source]

Renin-angiotensin system revisited

F. Fyhrquist
Abstract. New components and functions of the renin-angiotensin system (RAS) are still being unravelled. The classical RAS as it looked in the middle 1970s consisted of circulating renin, acting on angiotensinogen to produce angiotensin I, which in turn was converted into angiotensin II (Ang II) by angiotensin-converting enzyme (ACE). Ang II, still considered the main effector of RAS was believed to act only as a circulating hormone via angiotensin receptors, AT1 and AT2. Since then, an expanded view of RAS has gradually emerged. Local tissue RAS systems have been identified in most organs. Recently, evidence for an intracellular RAS has been reported. The new expanded view of RAS therefore covers both endocrine, paracrine and intracrine functions. Other peptides of RAS have been shown to have biological actions; angiotensin 2,8 heptapeptide (Ang III) has actions similar to those of Ang II. Further, the angiotensin 3,8 hexapeptide (Ang IV) exerts its actions via insulin-regulated amino peptidase receptors. Finally, angiotensin 1,7 (Ang 1,7) acts via mas receptors. The discovery of another ACE2 was an important complement to this picture. The recent discovery of renin receptors has made our view of RAS unexpectedly complex and multilayered. The importance of RAS in cardiovascular disease has been demonstrated by the clinical benefits of ACE inhibitors and AT1 receptor blockers. Great expectations are now generated by the introduction of renin inhibitors. Indeed, RAS regulates much more and diverse physiological functions than previously believed. [source]

Involvement of the somatostatin-2 receptor in the anti-convulsant effect of angiotensin IV against pilocarpine-induced limbic seizures in rats

Bart Stragier
Abstract The anti-convulsant properties of angiotensin IV (Ang IV), an inhibitor of insulin-regulated aminopeptidase (IRAP) and somatostatin-14, a substrate of IRAP, were evaluated in the acute pilocarpine rat seizure model. Simultaneously, the neurochemical changes in the hippocampus were monitored using in vivo microdialysis. Intracerebroventricularly (i.c.v.) administered Ang IV or somatostatin-14 caused a significant increase in the hippocampal extracellular dopamine and serotonin levels and protected rats against pilocarpine-induced seizures. These effects of Ang IV were both blocked by concomitant i.c.v. administration of the somatostatin receptor-2 antagonist cyanamid 154806. These results reveal a possible role for dopamine and serotonin in the anti-convulsant effect of Ang IV and somatostatin-14. Our study suggests that the ability of Ang IV to inhibit pilocarpine-induced convulsions is dependent on somatostatin receptor-2 activation, and is possibly mediated via the inhibition of IRAP resulting in an elevated concentration of somatostatin-14 in the brain. [source]