[Angiotensin II decreases atrial natriuretic peptide-induced cyclic GMP accumulation in rat glomerular mesangial cells].
Glomerular mesangial cells are believed to contribute to regulation of glomerular filtration rate through their contractility, which is regulated by various vasoactive hormones such as angiotensin II (A II), and atrial natriuretic peptide (ANP). A II has been recently reported to inhibit ANP-induced cyclic GMP (cGMP) accumulation in vascular smooth muscle cells, and other types of cells, but the mechanism of this inhibitory effect of A II is still unclear. In order to know the interaction between A II and ANP in glomerular mesangial cells and to know the mechanism of the interaction, I examined the effects of A II on ANP-induced cGMP accumulation in cultured rat glomerular mesangial cells. ANP produced rapid increase in cellular cGMP in cultured rat glomerular mesangial cells, which was significantly inhibited by co-incubation with A II. A II also inhibited cGMP accumulation produced by sodium nitroprusside, soluble guanylate cyclase activator. This inhibitory effect of A II was completely blocked by 1 mM of 3-isobutyl-1-methylxanthine (IBMX), a cyclic nucleotide phosphodiesterase inhibitor. Thus, it seems that A II inhibits ANP-induced cGMP accumulation by activating phosphodiesterase rather than by inhibiting guanylate cyclase. Since the action of A II has been reported to be mediated by increase of cytosolic free Ca2+ secondary to inositol 1,4,5-trisphosphate (IP3) generation and activation of protein kinase C secondary to diacylglycerol (DG) generation, I investigated the effects of Ca ionophore (A23187), and 12-O-tetradecanoyl phorbol-13-acetate (TPA), protein kinase C activator, on ANP-induced cGMP accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Maeda
S
S
Third Department of Medicine, Shiga University of Medical Science, Japan.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D006152:Cyclic GMP / Q000378:metabolism*; D003864:Depression, Chemical; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP