CGMP MEDIATES THE DESENSITIZATION TO BRADYKININ IN ISOLATED CANINE CORONARY-ARTERIES

The relaxation to bradykinin in canine coronary arteries is mediated b y endothelium-derived nitric oxide (NO) and hyperpolarizing factor (ED HF). 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 F-2 alpha and concentration-relaxation curves to bradykinin were obtained in con trol and desensitized arteries treated with indomethacin. After desens itization, there was a shift to the right of the concentration-relaxat ion curves to bradykinin. However, the elevation in guanosine 3',5'-cy clic monophosphate (cGMP) levels evoked by bradykinin was similar in b oth groups of tissues. The curves to bradykinin obtained in the presen ce of N-G-nitro-L-arginine (an NO synthase inhibitor) were depressed, whereas those obtained in arteries contracted with potassium (to elimi nate the EDHF-mediated relaxation) were not affected by the desensitiz ation. Addition of N-G-nitro-L-arginine, oxyhemoglobin, or methylene b lue before the desensitization procedure preserved, whereas S-morpholi nosydnonimine (SIN-1, a donor of NO) and 8-bromoguanosine 3',5'-cyclic monophosphate impaired, the EDHF-mediated relaxation to bradykinin. T hus the selective impairment of the EDHF-dependent relaxation to brady kinin may be mediated by NO, acting mainly through increased productio n of cGMP.