Comparative analysis of vasodilating mechanisms of Ki1769, Ki3315 and KRN2391, pyridinecarboximidamide derivatives, in porcine isolated coronary artery.
1. The vasodilating mechanisms of pyridinecarboximidamide derivatives which have a nitroxyl group (KRN2391), a phenyl group (Ki1769) or a hydroxyl group (Ki3315) were studied in porcine isolated coronary artery. 2. KRN2391 (10(-6) M) increased cyclic GMP formation but did not affect intracellular cyclic AMP level. Ki1769 (10(-5) M) and Ki3315 (10(-3) M) had no effect on intracellular cyclic GMP and cyclic AMP levels. 3. Despite producing submaximal relaxation at KRN2391 (10(-6) M) and nitroglycerin (10(-6) M), the increase in cyclic GMP caused by KRN2391 was lower than that caused by nitroglycerin. 4. Methylene blue (10(-5) M) inhibited KRN2391- and nitroglycerin-induced relaxations but did not affect Ki1769- and Ki3315-induced relaxation. 5. Glibenclamide (10(-6) M) inhibited KRN2391-, Ki1769- and Ki3315-induced relaxation but did not affect nitroglycerin-induced relaxation. 6. These results suggest that the nitroxyl group of KRN239 contributes to its nitrate action and the pyridinecarboximidamide moiety plays an important role of developing a K channel opening action.
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan.
T
T
Yokoyama
Y
Y
Okada
Y
Y
Jinno
H
H
Izumi
T
T
Izawa
N
N
Ogawa
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D006152:Cyclic GMP / Q000096:biosynthesis; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D011725:Pyridines; D014665:Vasodilator Agents; C084622:Ki 1769; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; C074245:KI 3315; D006152:Cyclic GMP; D005905:Glyburide; D008751:Methylene Blue