caa a22 4500 47707197X CHVBK 20180405111428.0 cr unu---uuuuu 170330e19960301xx s 000 0 eng 10.1007/BF00051127 doi (NATIONALLICENCE)springer-10.1007/BF00051127 Tilisolol hydrochloride dilates coronary arteries through an ATP-sensitive K+-channel opening mechanism in dogs [Elektronische Daten] [Quan Liu, Ichiro Nakae, Masayuki Takahashi, Atsushi Takaoka, Masahiko Kinoshita] Summary: Tilisolol is a beta-blocking agent with vasodilatory properties that was recently shown to possess a potassium (K+) channel opening activity. We investigated whether tilisolol has vasodilatory effects on coronary circulation in dogs. Mongrel dogs were chronically instrumented for measurements of circumflex coronary artery diameter (CoD) and coronary blood flow (CBF). We compared the effects of tilisolol on dog coronary arteries with those of two beta-blockers, propranolol and arotinolol. Both propranolol (1 mg/kg, intravenously, IV) and arotinolol (0.25 mg/kg, IV) decreased CoD and increased coronary vascular resistance (CVR). Tilisolol (2 mg/kg, IV) decreased CVR but had no significant effect on CoD. To investigate the mechanism of the coronary action of tilisolol, we examined differences in the response to tilisolol in the absence and presence of glibenclamide, an ATP-sensitive K+ channel blocker. Tilisolol (1,2,4 and 8 mg/kg, IV) produced a dose-dependent decrease in CVR without glibenclamide, whereas pretreatment with glibenclamide significantly suppressed this effect. Without glibenclamide, tilisolol had no significant effect on CoD at doses of 1-4 mg/kg (IV). However, at the higher dose of 8 mg/kg (IV), tilisolol significantly increased CoD (1.00±0.15%, p<0.01). After pretreatment with glibenclamide, tilisolol (1-8 mg/kg, IV) produced a significant decrease in CoD. Therefore, we concluded that tilisolol exerts its vasodilatory effect on the coronary circulation through an ATP-sensitive K+ channel opening mechanism, and that its vasodilatory action is more prominent in coronary resistance vessels than in large coronary arteries. Kluwer Academic Publishers, 1996 tilisolol nationallicence beta-blocker nationallicence K+ channel nationallicence coronary circulation nationallicence dog nationallicence Liu Quan First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut Nakae Ichiro First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut Takahashi Masayuki First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut Takaoka Atsushi First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut Kinoshita Masahiko First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/1(1996-03-01), 23-30 0920-3206 10:1<23 1996 10 10557 https://doi.org/10.1007/BF00051127 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00051127 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liu Quan First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut NATIONALLICENCE 700 1- Nakae Ichiro First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut NATIONALLICENCE 700 1- Takahashi Masayuki First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut NATIONALLICENCE 700 1- Takaoka Atsushi First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut NATIONALLICENCE 700 1- Kinoshita Masahiko First Department of Internal Medicine, Shiga University of Medical Science, Seta, 520-21, Ohtsu, Japan aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/1(1996-03-01), 23-30 0920-3206 10:1<23 1996 10 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer