Contribution of cyclic GMP formation to KRN2391-induced relaxation in coronary artery of the pig.
1. In the present study, we investigated the relationship between relaxation and guanosine 3':5'-cyclic monophosphate (cyclic GMP) formation induced by KRN2391, compared with those induced by nicorandil and nitroglycerin, in the coronary artery of the pig. 2. KRN2391 (10(-8)-3 X 10(-5) M), nicorandil (10(-8)-3 X 10(-4) M) and nitroglycerin (10(-9)-10(-5) M) antagonized the contraction caused by 25 mM KCl in a concentration-dependent manner. 3. The concentration-relaxation curves for KRN2391, nicorandil and nitroglycerin shifted rightward in the presence of methylene blue (10(-5) M). 4. KRN2391 (10(-6) M), nicorandil (10(-4) M) and nitroglycerin (10(-6) M) induced an increased in cyclic GMP. 5. The magnitude of the shift of the concentration-relaxation curve caused by methylene blue and the increase in cyclic GMP with KRN2391 were lower than those with nicorandil and nitroglycerin. 6. The adenosine 3':5'-cyclic monophosphate (cyclic AMP) level was not increased by KRN2391 even at a concentration that produced full relaxation. 7. The present results suggest that KRN2391-induced relaxation in the coronary artery of the pig is partly due to the increase in cyclic GMP formation through the stimulation of guanylate cyclase.
Jinno
Y
Y
Pharmaceutical Research Laboratory of Kirin Brewery Co., Ltd., Gunma, Japan.
Kasai
H
H
Ohta
H
H
Nishikori
K
K
Fukushima
H
H
Ogawa
N
N
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D006152:Cyclic GMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D005996:Nitroglycerin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011725:Pyridines; D014665:Vasodilator Agents; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D009536:Niacinamide; D020108:Nicorandil; D005996:Nitroglycerin; D006152:Cyclic GMP