Mechanism of relaxations to C-type natriuretic peptide in veins.
C-type natriuretic peptide (CNP) is an endothelium-derived peptide that shares structural homology with atrial natriuretic peptide (ANP). CNP causes greater endothelium-independent relaxations in veins compared with arteries. Relaxations to CNP in porcine coronary arteries are mediated by hyperpolarization of the smooth muscle membrane. Experiments were designed to investigate the mechanism(s) by which CNP causes relaxation in canine femoral veins. Rings of canine femoral veins without endothelium were suspended for measurement of isometric force in organ chambers. Concentration-response curves to CNP were obtained in veins contracted with either endothelin-1 (10(-8) M), KCl (40 mM), phenylephrine (10(-6) M) or prostaglandin F2 alpha (2 x 10(-6) M) in the absence and presence of BQ-123 (10(-6) M), NG-monomenthyl-L-arginine (L-NMMA; 10(-4) M), HS-142-1 (10(-5) M), methylene blue (10(-5) M), or potassium channel blockers, tetraethylammonium chloride (TEA; 10(-3) M), charybdotoxin (10(-7) M), glibenclamide (10(-7) M), or apamin (10(-7) M). Relaxations to CNP were significantly attenuated when the tissue was contracted with KCl and endothelin-1. During contraction to either phenylephrine or prostaglandin F2 alpha, relaxations to CNP were inhibited by HS-142-1, methylene blue, TEA, and charybdotoxin, but not by L-NMMA, glibenclamide, or apamin. In separate experiments, guanosine 3',5'-cyclic monophosphate increased twofold within 10-60 s after the addition of CNP (10(-8) M). These data suggest that CNP mediates relaxation of canine femoral veins through activation of large-conduction, calcium-activated potassium channels and activation of particulate and soluble guanylate cyclase.
Banks
M
M
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Wei
C M
CM
Kim
C H
CH
Burnett
J C
JC
Miller
V M
VM
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D005260:Female; D005268:Femoral Vein / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020098:Natriuretic Peptide, C-Type; D011506:Proteins / Q000494:pharmacology*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
D011506:Proteins; D014662:Vasoconstrictor Agents; D020098:Natriuretic Peptide, C-Type; D006152:Cyclic GMP