Co-operation between particulate and soluble guanylyl cyclase systems in the rat renal glomeruli

ANP and NO act via different receptors, although inducing the common intrac ellular messenger - cyclic GMP. However, interaction between both factors r emains unclear. Our observations suggested that in the rat kidney glomeruli , activities of the ANP- and NO-dependent guanylyl cyclase systems may be m utually compensated. To check this, we have tested effects of ANP and sodiu m nitroprusside (SNP) on cGMP synthesis and relaxation of glomeruli contrac ted with angiotensin II. The glomeruli were isolated from Wistar rats recei ving saline (Control), dexamethasone (DEX), deoxycorticosterone (DOCA) or N -omega-nitro-L-arginine methyl ester (NAME) for 1 or 2 days. In the DEX glo meruli exposed to 100 mu M SNP, rate of cGMP synthesis was significantly hi gher then in the Control (26.3 vs 16.0 pmol/mg.prot./2min., P < 0.05), whil e 1 mu M ANP was markedly less effective (2.8 vs 16.7 pmol/mg.prot./2min in Control, P < 0.01). On the contrary, in NAME group 1 mu M ANP stimulated c GMP synthesis up to 35.6 pmol/mg.prot./2min whereas efficacy of SNP was sli ghtly suppressed. High correlation coefficient (r = 0.979, p < 0.01) indica tes interrelationship between NO- and ANP-dependent cGMP synthesis. Ability of the glomeruli to relax in response to ANP or SNP was in accord to their ability to cGMP generation. This was confirmed by high correlation (r = 0. 845, p < 0.001) between degree of relaxation and rate of cGMP synthesis. Ou r results support strongly the hypothesis that both, ANP and NO dependent s ystems co-operate in regulation of the function of kidney glomeruli.