Atrial natriuretic peptides inhibit protein kinase C activation in rat aortic smooth muscle.
The effects of synthetic atrial natriuretic peptide and a cyclic guanosine 3',5'-monophosphate analogue, 8-bromo cGMP, on protein kinase C activation in rat aortic smooth muscle from spontaneously hypertensive and control Wistar-Kyoto rats were examined. Both atrial natriuretic peptide and 8-bromo cGMP inhibited protein kinase C activation by phenylephrine, an alpha 1-adrenoceptor agonist. When phorbol 12,13-dibutyrate was used, a substance which bypasses phospholipase C activation and directly activates protein kinase C, only atrial natriuretic peptide was effective in inhibiting activation. Additionally, it was found that spontaneously hypertensive rat aorta showed significantly greater basal and stimulated levels of protein kinase C in comparison with Wistar-Kyoto rat aorta. The results suggest first, a defective protein kinase C system in hypertensive rats and that atrial natriuretic peptide attenuates protein kinase C activation through cGMP-dependent and cGMP-independent mechanisms. This inhibition of protein kinase C activity may then lead to vasorelaxation.
Sauro
M D
MD
Dept. of Pharmacology and Therapeutics, University of South Florida, Tampa 33612.
Fitzpatrick
D F
DF
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010446:Peptide Fragments; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D010446:Peptide Fragments; D010656:Phenylephrine; C062525:atrial natriuretic factor prohormone (103-126); D015240:Phorbol 12,13-Dibutyrate; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D006152:Cyclic GMP