Cromakalim and cicletanine against pacing-induced myocardial ischemia in conscious rabbits.
Myocardial ischemia assessed by intracavital ST-segment elevation, shortening of ventricular effective refractory period (VERP), and increase in left ventricular end-diastolic pressure (LVEDP) was provoked by ventricular overdrive pacing (VOP) in conscious rabbits. Cromakalim (10 micrograms/kg), an ATP-sensitive K+ channel opener, and cicletanine (30 mg/kg), a cGMP-phosphodiesterase inhibitor, reduced VOP-induced ST-segment elevation and LVEDP-increase. Under resting conditions, cromakalim lowered blood pressure, increased heart rate (HR), and shortened VERP, whereas cicletanine decreased HR, prolonged VERP without changing blood pressure. Co-administration of cromakalim and cicletanine additively reduced VOP-induced ST-segment elevation, shortening of VERP, and LVEDP-increase. Cicletanine did not change cromakalim-induced hypotension but abolished reflexogenic tachycardia. This suggests that VERP shortening is not a prerequisite for the anti-ischemic effect of cromakalim, and the combination of these drugs may afford a potent and safe anti-ischemic effect without affecting hypotension induced cromakalim.
Szilvassy
Z
Z
First Department of Medicine, Albert Szent-Györgyi University Medical School of Szeged, Hungary.
Koltai
M
M
Ferdinandy
P
P
Jakab
I
I
Lonovics
J
J
Tarrade
T
T
Allard
M
M
Braquet
P G
PG
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003243:Consciousness; D019806:Cromakalim; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D015221:Potassium Channels / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D001578:Benzopyrans; D015221:Potassium Channels; D011725:Pyridines; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C038068:cicletanine