Subpressor infusions of angiotensin II alter glomerular binding, prostaglandin E2, and cyclic AMP production.
Angiotensin II (ANG II) has been postulated to have pathogenetic role in diminished glomerular function in a number of animal models of acute renal failure. The present studies were designed to test the hypothesis that modest elevations in circulating ANG II potentiate the ability of ANG II to reduce glomerular capillary surface area through an effect on ANG II binding to glomerular mesangial cells and/or influences on other modulators of function. Rat glomeruli isolated by a sieving technique were employed in vitro in an ANG II radioreceptor assay. Subpressor infusion of ANG II for 36 hours in rats increases the affinity and number of ANG II binding sites of isolated glomeruli. The ability of ANG II to influence function was tested by assessing its effect on glomerular surface area in vitro by image-analysis microscopy, a method of measuring mesangial cell contractility. The sensitivity and magnitude of ANG II-induced decrements in glomerular surface area were increased. ANG II infusion diminished glomerular prostaglandin E2 (PGE2) production, increased basal cyclic adenosine 3',5'-monophosphate (cAMP) production, and enhanced ANG II-induced decrements in cAMP production. In control glomeruli, only pharmacological concentrations of ANG II inhibited cAMP, but after ANG II infusion, physiological concentrations of ANG II were capable of inhibiting cAMP by as much as 57% (below basal values). In conclusion, continuous infusion of subpressor concentrations of ANG II in rats enhances the contractile response of the glomerular mesangial cell through effects on the cell's surface receptor for ANG II and on prostaglandin and cAMP production. These actions may be important mediators of the effects of ANG II on glomerular function associated with a number of experimental models of kidney disease.
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis*; D015232:Dinoprostone; D007678:Kidney Glomerulus / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism; D012083:Renin / Q000097:blood
D011458:Prostaglandins E; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000450:Aldosterone; D000242:Cyclic AMP; D012083:Renin; D015232:Dinoprostone