Evidence for lack of a role of cGMP in effect of alpha-hANP on aldosterone inhibition.
To investigate the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the inhibitory effect on aldosterone production of alpha-human atrial natriuretic polypeptide (alpha-hANP) we first compared the effects of the peptide with those of sodium nitroprusside (SNP) on the production of aldosterone and cGMP in dispersed adrenal capsular cells of rats, second, examined the effects of derivatives of cGMP on the production of aldosterone, and, third, studied the influence of potassium on the effects of alpha-hANP on the production of aldosterone and cGMP. alpha-hANP at concentrations of 3 X 10(-8) to 3 X 10(-7) M decreased the production of aldosterone in a dose-dependent manner, while markedly increasing the production of cGMP. On the other hand, although SNP at concentrations of 10(-5) to 10(-3) M increased the production of cGMP in a dose-dependent manner, it caused no significant changes in the production of aldosterone. Neither dibutyryl cGMP nor 8-bromo-cGMP affected the production of aldosterone in the adrenal cells. Although the aldosterone-inhibitory effect of alpha-hANP was lost in the potassium-free medium, the cGMP-stimulatory effect of the peptide was not altered by adding potassium to the incubation medium at concentrations of 0-5 meq/l. These results suggest that cGMP plays a minor role in the inhibitory effect of alpha-hANP on the production of aldosterone and that the production of cGMP stimulated by the peptide is not directly involved in the decrease in aldosterone production in adrenal capsular cells of rats.
D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D005260:Female; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000451:Mineralocorticoid Receptor Antagonists; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D003995:Dibutyryl Cyclic GMP; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D011188:Potassium