Endothelin production in cultured vascular smooth muscle cells--modulation by the atrial, brain, and C-type natriuretic peptide system.
We examined the regulatory mechanisms of endothelin-1 (ET-1) production in cultured rat vascular smooth muscle cells (VSMC) with a special focus on the roles of protein kinase C (PKC)- and cyclic guanosine-3',5'-monophosphate (GMP)-mediated signaling systems. Effects of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP) on angiotensin II (Ang II)-, and arginine vasopressin (AVP)-induced production of ET-1 were examined in cultured rat aortic VSMC. Ang II and AVP stimulated ET-1 production in a concentration-dependent manner through angiotensin subtype 1 (AT1) and vasopressin subtype 1 (V1) receptors, respectively. The stimulatory effects of Ang II and AVP were markedly abolished in PKC-depleted cells. Rat ANP (1-28), rat BNP-45, and rat CNP-22 potently inhibited Ang II- and AVP-stimulated ET-1 production in a concentration-dependent manner, respectively. The inhibitory effect by CNP on ET-1 production was paralleled by an increase in the cellular level of cyclic GMR.8-Bromo cyclic GMP reduced the stimulated ET-1 production by Ang II and AVP. These results indicate that Ang II and AVP stimulate ET-1 production in cultured rat VSMC through AT1 and V1 receptors by a mechanism probably involving activation of PKC, and that ANP, BNP, and CNP inhibit this stimulated production through a cyclic GMP-dependent process.
Hanehira
T
T
First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Kohno
M
M
Yoshikawa
J
J
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D016232:Endothelins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D016232:Endothelins; D004791:Enzyme Inhibitors; D011506:Proteins; D000804:Angiotensin II; D001127:Arginine Vasopressin; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C