Negative chronotropic and inotropic effects of U-92032, a novel T-type Ca2+ channel blocker, on the isolated, blood-perfused dog atrium.
We investigated the effects of U-92032 ((7-((bis-4-fluorophenyl) methyl)-1-piperazinyl)-2-2(2-hydroxyethylamino)-4-(1-methylethyl)- 2,4, 6-cycloheptatrien-1-one), a novel T-type Ca2+ channel blocker, on sinus rate and atrial contractile force in the isolated, blood-perfused atrium of the dog. U-92032 (1 to 300 nmol) induced negative chronotropic and inotropic responses in a dose-dependent manner, and the percentage decrease in sinus rate was less than that in atrial contractile force. Atropine did not affect the negative responses to U-92032. These results suggest that U-92032, a T-type Ca2+ channel blocker, simultaneously decreases the sinus rate and atrial force as do L-type Ca2+ channel blockers in the isolated dog atrium.
Lakhe
M
M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Yonezawa
T
T
Nagashima
Y
Y
Hirose
M
M
Chiba
S
S
D000704:Analysis of Variance; D000818:Animals; D016275:Atrial Function; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D015425:Myocardial Reperfusion; D010879:Piperazines / Q000494:pharmacology*; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010879:Piperazines; C086422:U 92032; D014334:Tropolone