Biosynthesis and physio-pharmacological actions of angiotensin peptides: 1. Synthetic enzymes.

The present work introduces a brief review of the actual knowledge concerning the enzymes involved in the biosynthesis of the active angiotensins, followed by a presentation of their main physio-pharmacological actions. The enzymatic pathways that generate active ang. II (1-8) are complemented with data concerning its transformation into angiotensin III (2-8), ang. IV (3-8), ang. V (1-5) and ang. 1-7. Besides the classic renin of renal origin, the tissue isorenins, represented by tonin and cathepsins D and G, inactive angiotensin-I-forming are also reviewed. Furthermore, chymase and the new angiotensin-converting enzyme 2 (ACE2), which generates angiotensin 1-7, having opposite properties from the mother-substance (Ang. II) are discussed at length. The presentation of properties of angiotensin-generating enzymes is followed by the presentation of the action of angiotensinases (aminopetidases, carboxypeptidase and endopeptidases), which are involved both in the generation of biologically active angiotensin peptides and in their inactivation.

Comparative study of the inhibitory effects of adrenomedullin on angiotensin II contraction in rat conductance and resistance arteries.

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.

New technical approaches in stereotaxic catheterization of cerebral ventriculi: implications for the L-arginine/NO synthase/nitric oxide cascade.

In order to study the actions of certain substances at cerebral level, a stereotactic device for ensuring a precise catheterization of points in certain cerebral areas was used. For the operation technique was used a stereotaxic atlas specifically designed for rat brain (G. Paxinos, C. Watson, 1998), which offers all the necessary information for the identification of the trepanation. Stereotaxic implantation of cannules in the brain is useful for microinjecting solutions containing various substances (in amounts of microl), directly and targeted in the anatomical structures of the brain. The technique described can use either metalic or silastic cannules, that have variable lumen (usually for adapting a Hamilton syringe). The cannules can be implanted at cerebroventricular level, having the possibility to target all the cerebral ventricles. The intracerebroventricular (icv) administration of L-arginine induces a significant increase of response latency for mechano-algesic test. The most obvious changes are induced following the administration of the association of L-NAME with L-arginine, situation when is manifested an important increase of the response latency, starting with 5 minutes post-administration and continuing up to 45 minutes determination. The increase is significantly higher compared with the results obtained with L-arginine alone. A similar evolution is registered in the case of the plantar test.