Effects of glibenclamide and nicorandil in post-ischaemic contractile dysfunction of perfused hearts in normotensive and spontaneously hypertensive rats.
OBJECTIVE
We have demonstrated previously that nicorandil, an ATP-sensitive potassium channel opener, improved post-ischaemic contractile dysfunction of perfused hearts in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats dose-dependently. This study aimed to characterize the effect of glibenclamide, an ATP-sensitive potassium channel blocker, and nicorandil in post-ischaemic contractile dysfunction of SHR and WKY rats.


METHODS
The perfused hearts were subjected to 30 min of global ischaemia and then 30 min of reperfusion. Administration of 10 or 50 mumol/l glibenclamide or of a combination of glibenclamide and 300 mumol/l nicorandil was performed for 10 min before the ischaemia. The left ventricular developed pressure and end-diastolic pressure were measured.


RESULTS
Postischaemic contractile function was better in WKY rats than it was in SHR. Neither glibenclamide nor a combination of glibenclamide and nicorandil influenced the postischaemic contractile function or increased the incidence of reperfusion arrhythmias. The recoveries of coronary flow and heart rate after reperfusion were poor and the incidence of reperfusion arrhythmias was low in SHR.


CONCLUSIONS
These results suggest that nicorandil improves postischaemic contractile dysfunction via a mechanism involving ATP-sensitive potassium channel opening both in SHR and in WKY rats. The hypertensive hearts were more susceptible to cardiac reperfusion dysfunction, compared with normal hearts.
Nakagawa
C
C
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Asayama
J
J
Tatsumi
T
T
Matoba
S
S
Kobara
M
M
Tanaka
T
T
Ohta
B
B
Kawahara
A
A
Tsuruyama
K
K
Katamura
M
M
Nakagawa
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002306:Cardiac Volume; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D009536:Niacinamide; D020108:Nicorandil; D003402:Creatine Kinase; D005905:Glyburide