Differential effects of celiprolol and atenolol on large epicardial coronary arteries in conscious dogs at rest and during exercise.
The effects of celiprolol (1 mg/kg), a selective beta 1-adrenoceptor antagonist with partial agonist activity (PAA), on large and small coronary arteries and on systemic hemodynamics were investigated and compared with those of atenolol (1 mg/kg) and saline at rest and during three levels of treadmill exercise in the same 7 conscious dogs. Control exercise after saline administration induced increases in heart rate (HR 131 +/- 4%), left ventricular (LVdP/dt 117 +/- 5%), coronary blood flow (CBF 133 +/- 13%), and circumflex artery diameter (CxAD, 6.6 +/- 1.3%) and a decrease in coronary vascular resistance (CVR, -47 +/- 3%). Atenolol decreased LVdP/dt (-19 +/- 2%) and CxAD (-3.2 +/- 0.3%, p < 0.05) at rest, but large epicardial coronary arteries remained constricted during exercise (-4.7 +/- 1.4% at 12 km/h, p < 0.05) despite simultaneous dilation of coronary resistance vessels. In contrast to atenolol, celiprolol did not constrict large coronary arteries at rest (CxAD -0.2 +/- 0.9%, NS), and this beneficial effect of celiprolol was maintained throughout the exercise period. LVdP/dt was not modified and HR was slightly increased (14.3 +/- 2.6%) at rest by celiprolol. Atenolol and celiprolol reduced the exercise-induced positive inotropic and chronotropic effects, atenolol being the most potent. Thus, in dogs at rest when basal sympathetic tone was low, celiprolol, most likely because of its PAA, induced slight cardiac stimulation and prevented vasoconstriction of the large coronary arteries usually observed after beta-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Drieu la Rochelle
C
C
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Giudicelli
J F
JF
Berdeaux
A
A
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D017272:Celiprolol / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D010496:Pericardium; D010805:Physical Conditioning, Animal; D012146:Rest
D001262:Atenolol; D017272:Celiprolol