Mechanism of relaxations to c-type natriuretic peptide in
veins.
Banks, Michelle, Chi-Ming Wei, Cheol H. Kim, John C. Burnett, Jr., and
Virginia M. Miller.
Departments of Surgery and Physiology and Biophysics and the
Cardiorenal Research Laboratory, Mayo Clinic and Foundation,
Rochester, MN
APStracts 3:0176H, 1996.
C-type natriuretic peptide (CNP) is an endothelium-derived peptide
which shares structural homology with atrial natriuretic peptide
(ANP). CNP causes greater endothelium-independent relaxations in
veins compared to 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 (10-8M), KCl (40mM), phenylephrine (10-6M) or
prostaglandin F2[alpha] (2x10-6M) in the absence and presence of BQ
123 (10-6M), NG-monomenthyl-L-arginine (L-NMMA; 10-4M), HS-142-1 (10
-5M), methylene blue (10-5M), or potassium channel blockers,
tetraethylammonium chloride (TEA; 10-3M), charybdotoxin (10-7M),
glibenclamide (10-7M), or apamin (10-7M). 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, cGMP increased two
-fold within 10-60 seconds after the addition of CNP (10-8M). These
data suggest that CNP mediates relaxation of canine femoral veins
through activation of high conduction calcium activated potassium
channels and activation of particulate and soluble guanylate cyclase.
Received 1 March 1995; accepted in final form 15 April 1996.
APS Manuscript Number H199-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96