Comparative analysis of vasodilating Mechanisms of Kil769, Ki3315 and KRN2391, pyridinecarboximidamide derivatives, in porcine isolated coronary artery

Article

作者: Okada, Yuji ; Izawa, Toshio ; Jinno, Yasuhiro ; Izumi, Hideakira ; Yokoyama, Takashi ; Ogawa, Nobuyuki

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.

1993-11-01·European Journal of Pharmacology3区 · 医学

Effects of KRN2391, a novel vasodilator, on pancreatic exocrine secretion in anesthetized dogs

3区 · 医学

Article

作者: Lei-Ming Ren ; Akira Horiuchi ; Kazuhiko Iwatsuki ; Shigetoshi Chiba

The effects of KRN2391, a newly synthesized vasodilator, on pancreatic exocrine secretion in anesthetized dogs were compared with those of Ki3315, pinacidil and nitroprusside. Graded doses of KRN2391 (0.03-3 mumol/kg) and nitroprusside (0.003-0.3 mumol/kg) injected i.a. produced dose-dependent increases in the secretion of pancreatic juice, with a high concentration of protein and low concentration of bicarbonate, but Ki3315 or pinacidil did not (up to 10 mumol/kg). KRN2391 and nitroprusside increased the cyclic GMP levels in pancreatic tissue together with the increase in pancreatic secretion. Methylene blue decreased pancreatic secretion and cyclic GMP levels stimulated by KRN2391 and nitroprusside, but glibenclamide did not. KRN2391, Ki3315, pinacidil and nitroprusside caused vasodilator actions. These results suggest that KRN2391 has direct secretory properties on pancreatic exocrine glands of the dog and its nitro moiety has an important role in the stimulation of pancreatic secretion, but the K+ channel opening action or increasing of blood flow rate does not participate in the secretion.

1993-09-01·European Journal of Pharmacology3区 · 医学

Vasorelaxant action of Ki1769, a new pyridinecarboximidamide, in isolated porcine coronary artery

3区 · 医学

Article

作者: Yuji Okada ; Hideaki Fukushima ; Tomoko Kashiwabara ; Nobuyuki Ogawa ; Yasuhiro Jinno ; Toshio Izawa ; Takashi Yokoyama

The characteristics of KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethansulfonate) and its phenethyl and 2-hydroxyethyl derivatives (Ki1769 and Ki3315) were studied in isolated porcine coronary arteries. KRN2391, Ki1769 and Ki3315 produced concentration-dependent relaxation of coronary arteries contracted by 25 mM KCl and the order of relaxant potency was KRN2391 > Ki1769 > Ki3315. At the maximum effect, KRN2391 produced nearly complete relaxation but Ki1769 produced about 66% relaxation. The maximum effect of Ki3315 could not be obtained because of its solubility. The relaxation induced by KRN2391 was antagonized by glibenclamide and methylene blue but relaxations caused by Ki1769 and Ki3315 were antagonized by glibenclamide alone. The antagonistic effect of glibenclamide on Ki1769- and Ki3315-induced relaxations was more potent than that on KRN2391-induced relaxation. KRN2391 induced relaxation of coronary arteries contracted by 40 mM KCl in a concentration-dependent manner but the effect of KRN2391 was smaller against 40 mM KCl-induced contractions than against 25 mM KCl-induced contractions. Ki1769 had almost no effect on coronary arteries contracted by 40 mM KCl. These results suggest that pyridinecarboximidamide derivatives which do not possess a nitroxyl group have vasodilating ability based on a K+ channel opening action.

100 项与 KI-3315 相关的药物交易

登录后查看更多信息