ABSTRACT
Biochemical, physiological and functional studies suggest that the brain renin-angiotensin system (RAS) is regulated independently of the peripheral RAS. Also, all enzymes and peptides necessary for the biosynthesis of various angiotensins have been recognized within the central nervous system. There are divergent opinions concerning the localization of the different components of this system which is not fully understood. It is believed that central actions of angiotensins are not exclusively associated with their traditional roles, many studies showing that central angiotensins are also involved in learning and memory processes. Moreover, clinical trials and studies on animal models suggest that pharmacological manipulation of angiotensin ligands may be of clinical importance in slowing or even stopping the cognitive deterioration seen in vascular dementia and Alzheimer's disease.
Subject(s)
Brain/physiopathology , Cognition/physiology , Dementia , Nootropic Agents/pharmacology , Renin-Angiotensin System/physiology , Animals , Dementia/drug therapy , Dementia/physiopathology , Dementia/prevention & control , HumansABSTRACT
The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has emerged that angiotensin II (Ang II) is not the only biologically active peptide generated by the RAS. At least three others have been identified: the heptapeptide Ang III, the hexapeptide Ang IV and Ang 1-7. Specific receptors exits for the last two peptides. In addition, the range of possible physiological and pathophysiological properties for Ang II has been expanding. The current perception of the RAS is therefore that of a much more complex system than previously believed, with autocrine, paracrine and endocrine properties extending beyond the cardiovascular system. This mini-review focuses on the synthetic pathways of the Ang peptides and describes some of their pleiotropic actions.
Subject(s)
Aldosterone/physiology , Angiotensins/pharmacology , Peptide Fragments/pharmacology , Renin-Angiotensin System/physiology , Angiotensin II/pharmacology , Angiotensins/chemistry , Animals , Cardiovascular Physiological Phenomena , HumansABSTRACT
Adrenomedullin (ADM), a ubiquitous vasoactive peptide, has been the target of a multitude of studies concerning its effect on the vascular tone. The present work aims at clarifying a series of its interactions with the renin-angiotensin system. The study uses the rat aorta ring as a model of conductance vessels, with or without vascular endothelium, and the second order branch of rat mesenteric arteries as a model of resistance arteries. Interactions between various concentrations of ADM and angiotensin II (Ang II) were studied, in the presence of L-NAME (a nitric oxide [NO] synthase inhibitor) and methylene blue (MB; a soluble guanylate cyclase inhibitor). Results point out differences in the mechanism of the inhibitory action of ADM upon Ang II effects in the two vessel types studied. Inhibition of Ang II contraction by ADM involves guanylate cyclase in both cases. However, NO is involved in ADM-induced inhibition of angiotensinergic vasoconstriction only in the conductance arteries, not in the resistance ones.
Subject(s)
Angiotensin II/pharmacology , Aorta, Thoracic/drug effects , Mesenteric Arteries/drug effects , Peptides/pharmacology , Vasoconstrictor Agents/pharmacology , Adrenomedullin , Animals , Aorta, Thoracic/physiology , Drug Interactions , Enzyme Inhibitors/pharmacology , In Vitro Techniques , Male , Mesenteric Arteries/physiology , NG-Nitroarginine Methyl Ester/pharmacology , Phenylephrine/pharmacology , Potassium/pharmacology , Rats , Rats, Wistar , Vascular Resistance/drug effects , Vasoconstriction/drug effectsABSTRACT
Using isolated rat aortic rings perfused with Krebs-Henseleit saline, the vascular effects of angiotensin (1-7) (Ang [1-7]) and its interactions with angiotensin II (Ang II) were investigated. Ang (1-7) induced endothelium-dependent relaxation and vasodilating effects in preparations precontracted with phenylephrine. Without preconstriction, Ang (1-7) at high doses (10(-6) 10(-5) M) produced either a significant inhibition of Ang II-induced vasoconstriction or a non-tachyphylactic vasopressor response. While losartan inhibited the vasoconstriction induced by Ang (1-7), A779 blocked only its relaxation. Unlike losartan, blockade of AT(2)-receptors with PD 123319 had no effect. Taking into account the biphasic effects of angiotensin (1-7), we propose that it is one of the active components of the renin-angiotensin system, which is involved as a modulator both in the counter-regulatory actions of Ang II and in the self-regulation of its own vasodilating effects.
