Gender and relaxation to C-type natriuretic peptide in porcine coronary arteries.
Experiments were designed to determine whether or not relaxations of coronary arterial smooth muscle to C-type natriuretic peptide (CNP) vary according to gender, and if so, to determine mechanisms for the differences. Rings of coronary arteries without endothelium from sexually mature male and female Yorkshire pigs were suspended in organ chambers for measurement of isometric force. Cumulative concentration-responses to CNP (10(-9)-10(-7) M) were obtained in the absence and presence of either K+ channel blockers (charybdotoxin, apamine, or glibenclamide, 10(-7) M) or the clearance-receptor antagonist C-ANP (10(-6) M) during contractions to prostaglandin F2alpha (2 microM). Relaxations to CNP were significantly less in arteries from male compared with female pigs and were significantly attenuated by charybdotoxin and glibenclamide in both sexes. However, apamine reduced relaxations to CNP only in arteries from female pigs. C-ANP significantly potentiated relaxations to CNP only in arteries from male pigs. In separate experiments, cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay at specified times after the addition of CNP (10(-7) M). Peak increases in cGMP were greater and occurred earlier in arteries from female than from male pigs; these differences were eliminated by the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (10(-4) M). These results demonstrate three mechanisms that contribute to gender differences in CNP-mediated relaxation of coronary arterial smooth muscle: activation of low conductance Ca2+-activated K+ channels, natriuretic peptide clearance receptors, and activity/regulation of phosphodiesterases.
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
D A
DA
Barber
J C
JC
Burnett
L A
LA
Fitzpatrick
G C
GC
Sieck
V M
VM
Miller
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020098:Natriuretic Peptide, C-Type; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011506:Proteins / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects / Q000378:metabolism; D012727:Sex Characteristics; D013552:Swine
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP