cGMP mediates the desensitization to bradykinin in isolated canine coronary arteries

L Olmos, JV Mombouli, S Illiano… - American Journal of …, 1995 - journals.physiology.org
L Olmos, JV Mombouli, S Illiano, PM Vanhoutte
American Journal of Physiology-Heart and Circulatory Physiology, 1995journals.physiology.org
The relaxation to bradykinin in canine coronary arteries is mediated by endothelium-derived
nitric oxide (NO) and hyperpolarizing factor (EDHF). Desensitization to the kinin was
induced by incubation of canine coronary arteries with endothelium with 10 (-8) M
bradykinin for 30 min. After washout, tissues were contracted with prostaglandin F2 alpha,
and concentration-relaxation curves to bradykinin were obtained in control and desensitized
arteries treated with indomethacin. After desensitization, there was a shift to the right of the …
The relaxation to bradykinin in canine coronary arteries is mediated by endothelium-derived nitric oxide (NO) and hyperpolarizing factor (EDHF). Desensitization to the kinin was induced by incubation of canine coronary arteries with endothelium with 10(-8) M bradykinin for 30 min. After washout, tissues were contracted with prostaglandin F2 alpha, and concentration-relaxation curves to bradykinin were obtained in control and desensitized arteries treated with indomethacin. After desensitization, there was a shift to the right of the concentration-relaxation curves to bradykinin. However, the elevation in guanosine 3',5'-cyclic monophosphate (cGMP) levels evoked by bradykinin was similar in both groups of tissues. The curves to bradykinin obtained in the presence of NG-nitro-L-arginine (an NO synthase inhibitor) were depressed, whereas those obtained in arteries contracted with potassium (to eliminate the EDHF-mediated relaxation) were not affected by the desensitization. Addition of NG-nitro-L-arginine, oxyhemoglobin, or methylene blue before the desensitization procedure preserved, whereas 3-morpholinosydnonimine (SIN-1, a donor of NO) and 8-bromoguanosine 3',5'-cyclic monophosphate impaired, the EDHF-mediated relaxation to bradykinin. Thus the selective impairment of the EDHF-dependent relaxation to bradykinin may be mediated by NO, acting mainly through increased production of cGMP.
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