angiotensin-iii and Cardiomegaly

From the myotropic and vasopressor activities of the numerous analogs of angiotensin II, it has been determined that the phenyl group of position 8 possesses the information for biologic response while the aromatic side groups in positions 4 and 6, the guanido group in position 2 and the C-terminal carboxyl are involved in binding to the receptor site. Removal of a side group of the C-terminal phenyalanine yields peptides that bind to the receptor. While many of these have low agonist properties, all have antagonist properties. Modifications in the aromatic side groups affect conformation of the octapeptide. This change may relate to receptor binding but sufficient data are not yet available to determine a correlation pattern. A proposed conformation for angiotensin is given as well as an artist's concept of angiotensin II binding to its membrane receptor utilizing the groups known to be involved in binding. Both angiotensin II and III [des-Asp] angiotensin II stimulate the biosynthesis and release of aldosterone from adrenal glomerulosa cells. Sufficient data are not yet available to determine whether the conversion of angiotensin II to angiotensin III is neccessary for the steroidogenesis activity.

Topics: Adrenal Glands; Angiotensin II; Angiotensin III; Angiotensin Receptor Antagonists; Blood Pressure; Cardiomegaly; Catecholamines; Protein Biosynthesis; Protein Conformation; Receptors, Angiotensin; Receptors, Cell Surface; Structure-Activity Relationship

The in vitro anti-hypertrophic and hyperplastic actions of des-aspartate-angiotensin I (DAA-I) on cultured cardiovascular cells have been demonstrated in earlier experiments. The present study investigated its effects on the development of neointima in balloon catheter-injured carotid artery of the Sprague-Dawley (SD) rat and the development of cardiovascular hypertrophy in the spontaneously hypertensive rat. Treatment with i.v. DAA-I for 14 days post-injury dose-dependently attenuated the development of neointima. The maximum effect was obtained at 34 pmol/kg/day. The data support the possibility that endogenous angiotensins could inhibit neointima growth. This opens up avenues for their therapeutic elevation in combating neointima-related restenosis of which current drugs are not fully effective in suppressing. Five-week-old pre-hypertensive SHR, when orally administered with a dose of 769 nmol/kg/day DAA-I for a duration of 47 weeks, showed significant reduction in the development of cardiac and vascular hypertrophy compared to the untreated controls. Similar treatment with DAA-I had no effect on the Wistar Kyoto rats. The present findings support the contention that, besides angiotensin II, other endogenous angiotensins are also involved in the regulation and/or pathophysiology of the cardiovascular system.

Topics: Angiotensin I; Angiotensin III; Animals; Arterial Occlusive Diseases; Arteriosclerosis; Cardiomegaly; Cardiomyopathy, Hypertrophic; Dose-Response Relationship, Drug; Hypertension; Injections, Intravenous; Male; Rats; Tunica Intima