Positive inotropic effect of nicorandil in adult rats in situ.
OBJECTIVE
Although the cardiac protective and negative inotropic effects of nicorandil via opening the sarcolemmal or mitochondrial K(ATP) channel and NO-like action are well known, positive inotropic effects of nicorandil in normal hearts have not been reported. The aim of the current study was to investigate how nicorandil affects left ventricular (LV) function of in situ adult rat hearts through the entire cardiovascular system.


METHODS
We performed simultaneous and continuous measurements of LV pressure (P) by a catheter-tip micromanometer and LV volume (V) using a conductance catheter. We obtained steady-state LV P-V loops and intermittent curvilinear LV end-systolic pressure-volume relations (ESPVRs), LV end-systolic pressure (ESP(mLVV)), and systolic pressure-volume area (PVA(mLVV)) at midrange LVV (mLVV). We evaluated the effects of nicorandil on LV function by these mechanical indexes sensitively reflecting changes in LV contractility and work capability, preload (end-diastolic volume, EDV), and afterload (effective arterial elastance, Ea).


RESULTS
Nicorandil (10 and 20 microg.kg(-1).min(-1)) (blood concentration: 0.53 +/- 0.14 and 1.48 +/- 0.21 microg/ml) largely shifted ESPVR upward and thus significantly increased ESP(0.06), PVA(0.06), stroke volume due to increase in EDV, and ejection fraction without significant changes in Ea and heart rate. In contrast, an NO donor, nitroglycerin (1 microg.kg(-1) . min(-1)), significantly decreased Ea but did not change ESP(0.06), PVA(0.06), and EDV. Furthermore, either a nonselective K(ATP) channel blocker, glybenclamide, or a mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, abolished these nicorandil-induced positive inotropic actions.


CONCLUSIONS
These results suggest that nicorandil exhibited positive inotropic actions on LV function of in situ hearts in adult rats with resultant increased preload (EDV).
Nakahashi
Kazuyoshi
K
Department of Physiology II, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan.
Kitagawa
Yutaka
Y
Ito
Haruo
H
Kuzumoto
Naoya
N
Furuya
Hitoshi
H
Takaki
Miyako
M
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001810:Blood Volume / Q000187:drug effects; D002316:Cardiotonic Agents; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D054086:KATP Channels; D008297:Male; D020108:Nicorandil / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D018528:ATP-Binding Cassette Transporters; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D014665:Vasodilator Agents; C092520:uK-ATP-1 potassium channel; D020108:Nicorandil; D005996:Nitroglycerin