cGMP mediates the desensitization to bradykinin in isolated canine coronary arteries.
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.
Olmos
L
L
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030.
Mombouli
J V
JV
Illiano
S
S
Vanhoutte
P M
PM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D006152:Cyclic GMP / Q000502:physiology*; D004285:Dogs; D004351:Drug Resistance; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019335:Nitroarginine; D010108:Oxyhemoglobins / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D010108:Oxyhemoglobins; D014665:Vasodilator Agents; D019335:Nitroarginine; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D006152:Cyclic GMP; D011188:Potassium; D001920:Bradykinin; D008751:Methylene Blue