Effects of atenolol, metroprolol, and pamatolol on cardiac and vascular beta-adrenoceptors in the rat.
Three beta-adrenoceptor antagonists--atenolol (A), metoprolol (M), and pamatolol (P)--were examined with respect to their effects on isoproterenol responses of isolated right atria and portal veins from rats. With all three blockers at concentrations of 10(-7), 10(-6), and 10(-5) M, the chronotropic atrial responses indicated a linear relation with slope of 1 for log (dose ratio - 1) versus log[blocker]. The following pA2 values were obtained: A = 7.14, M = 7.51, P = 7.56. Inhibition of spontaneous contractions in portal veins by isoproterenol was studied after alpha-adrenoceptor blockade by phenoxybenzamine. The beta-adrenoceptor antagonists were used at 10(-6), 10(-5), and 10(-4) M in these experiments. Only with P did the relation log (dose ratio-1) versus log[blocker] show a slope near unity, whereas A and M gave slopes significantly less than 1. Intercepts of the regression lines with the abscissa corresponded to pA2 values of A = 6.01, M = 6.51, P = 5.54. The results indicate that all three substances are "cardioselective" beta-adrenoceptor antagonists devoid of intrinsic beta-stimulatory action. A and M show a comparable degree of cardioselectivity, whereas P is more selective.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects*; D002219:Carbamates / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002219:Carbamates; D011412:Propanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C017601:pamatolol; D001262:Atenolol; D008790:Metoprolol