Mechanism of relaxations to dendroaspis natriuretic peptide in canine coronary arteries.
Experiments were designed to determine mechanisms by which Dendroaspis natriuretic peptide (DNP) causes relaxations in coronary arteries. Rings of canine left circumflex artery with and without endothelium were suspended in organ chambers filled with Krebs-Ringer bicarbonate solution (37 degrees C, bubbled with 95% O2/5% CO2). Concentration-response curves to DNP (10(-10) to 3 x 10(-7) M) were obtained in arteries contracted with prostaglandin (PGF(2alpha), 2 x 10(-6) M), either in the absence or the presence of C-ANP (10(-6) M) to inhibit natriuretic clearance receptors; indomethacin to inhibit cyclooxygenase (INDO, 10(-5) M), N(G)-monomethyl-L-arginine to inhibit production of nitric oxide (L-NMMA; 10(-4) M), HS-142-1 to inhibit particulate guanylate cyclase (10(-5) M); 1H-[1,2,4]oxadiazolo-[4,3-alpha]quinoxalin-1-one to inhibit soluble guanylate cyclase (ODQ; 10(-5) M), or tetraethylammonium to inhibit potassium channels (TEA; 10(-3) or 10(-2) M). Relaxations to DNP were greater in rings with than in those without endothelium. C-ANP significantly attenuated relaxations to DNP only in rings with endothelium. HS-146-1 but not INDO, L-NMMA, ODQ, and TEA significantly reduced relaxations to DNP in rings with and without endothelium contracted with PGF(2alpha). These results suggest that the endothelium augments inhibitory effects of DNP and that natriuretic clearance receptors mediate this component of the response to DNP in canine coronary arteries. In addition, relaxations to DNP in canine arterial smooth muscle involve activation of particulate guanylate cyclase but not hyperpolarization.
Collins
E
E
Department of Surgery, Physiology, and Biophysics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Bracamonte
M P
MP
Burnett
J C
JC
Miller
V M
VM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D017815:Elapidae; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D009320:Atrial Natriuretic Factor