Profile of cardiovascular effects of NKH477, a novel forskolin derivative, assessed in isolated, blood-perfused dog heart preparations: comparison with isoproterenol.
Cardiac and coronary vasodilator effects of NKH477, a novel water-soluble forskolin derivative, and isoproterenol, a nonselective beta-adrenoceptor full agonist, were compared in isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. Both agents were injected intraarterially. The two agents increased the force of contraction of the paced papillary muscle and of the unpaced muscle, and the rate of automaticity of the latter. They increased sinus rate and accelerated AV nodal conduction. In producing these cardiac effects, both agents were similar, although NKH477 was 120-350 times less potent than isoproterenol; however, NKH477 differed distinctly from isoproterenol in that the former increased coronary blood flow more greatly than the latter. Thus, NKH477 is more coronary vasodilatory than positive inotropic, and more positive inotropic than positive chronotropic. Such a cardiovascular profile of NKH477 was similar to that of forskolin, except for the duration of actions; NKH477 was longer-acting than forskolin.
Ishizuka
O
O
Research Laboratories, Pharmaceuticals Group, Nippon Kayaku, Tokyo, Japan.
Hosono
M
M
Nakamura
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D014665:Vasodilator Agents; D005576:Colforsin; D007545:Isoproterenol