Antiarrhythmic effects of selective beta 1- and beta 2- and nonselective beta-adrenoceptor blockade in normokalaemic and dietary-induced hypokalaemic rats.
Hypokalaemia (HK) is a risk factor for development of clinical arrhythmias, and epinephrine (Epi), released after myocardial infarction, may itself induce HK. The effects of selective beta 1- and beta 2-blockade with metoprolol (M) and ICI 118551 (I), respectively, and non-selective blockade with propranolol (P) against early ischaemia-induced arrhythmias were therefore compared in normokalaemic (NK) and dietary-induced HK rats. Plasma Epi, norepinephrine (NE), and K+ levels were also measured. All three blockers [5-10 mg/kg intravenously (i.v.)] were antifibrillatory in NK rats, whereas I and P (2-10 mg/kg) additionally reduced the number of ventricular premature beats. Coronary artery ligation increased plasma Epi levels in both NK an HK rats, but plasma NE increased further in HK rats. HK was also associated with an increased arrhythmia severity and negation of the antifibrillatory action of M. In contrast, I and P retained antiarrhythmic and antifibrillatory effects in HK animals and increased survival. Both I and P increased plasma K+ levels in both NK and HK animals whereas M did not. We concluded that beta 2-receptor-mediated HK after coronary occlusion may play a substantial role in arrhythmogenesis. Protection afforded by beta 2-blocking agents may be due to alleviation of HK in HK rats or to induction of hyperkalaemia in NK rats.
Winslow
E
E
Department of Pharmacology, Organon Laboratories, Lanarkshire, Scotland.
Walker
G
G
Mason
R
R
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003331:Coronary Vessels / Q000502:physiology; D004032:Diet; D006339:Heart Rate / Q000187:drug effects; D007008:Hypokalemia / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002395:Catecholamines; D011412:Propanolamines; C026777:ICI 118551; D011433:Propranolol; D008790:Metoprolol; D007545:Isoproterenol; D011188:Potassium