Differential antiarrhythmic potency of adenosine in normotensive and spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR) have functional defects in purinergic neurotransmission. Because adenosine is antiaarrhythmic, the adenosine probably has lesser antiarrhythmic potency in SHR. We tested this hypothesis by comparing the antiarrhythmic effects of adenosine against arrhythmias induced by global myocardial ischemia/reperfusion in isolated perfused heart of SHR and its normotensive counterparts: Wistar Kyoto rats (WKY) and Sprague-Dawley rats (SD). The Langendorff isolated perfused heart preparation was used. Ventricular fibrillation (VF) was induced by global myocardial ischemia/reperfusion. Ischemia/reperfusion-induced VF was most severe in SD. The severity of VF in WKY was similar to that in SHR. Adenosine 75 micrograms/heart had significant antiarrhythmic effect in both types of normotensive rats; a much higher dose of adenosine (150 micrograms/heart) was required to attenuate cardiac arrhythmias in SHR, suggesting reduced responsiveness to adenosine in genetically hypertensive rats. The mechanisms of action responsible for reduced responsiveness to adenosine in SHR require further study.
Tang
X L
XL
Department of Pharmacology, University of Hong Kong.
Cho
C H
CH
Wong
T M
TM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D000241:Adenosine