Differentiation of hemodynamic, humoral and metabolic responses to beta 1- and beta 2-adrenergic stimulation in man using atenolol and propranolol.
The respective contributions of beta-adrenoceptor subtypes to the hemodynamic, humoral and metabolic consequences of adrenergic stimulation during graded exercise in man were investigated using nonselective beta-adrenoceptor blockade with propranolol and beta 1-adrenoceptor blockade with atenolol. Doses of these agents that produced comparable suppression of beta 1 response as measured by antagonism of cardioacceleration during exercise were selected. Six healthy, nonsmoking males received these drugs in a placebo-controlled, Latin-square, randomized manner using a double-blind protocol. Both drugs produced comparable reductions of systolic blood pressure and elevation of diastolic blood pressure compared with placebo as exercise load increased. Propranolol produced higher peak epinephrine levels than atenolol or placebo (808 +/- 162, 640 +/- 190 and 584 +/- 153 pg/ml, respectively, p = 0.03), but norepinephrine levels did not show significant differences. Plasma renin activity was similarly suppressed both at rest and during all grades of exercise by both drugs. Lactate levels during moderate exercise were significantly lower after propranolol than after either atenolol or placebo (p = 0.03), but were similar at heavy work loads. Plasma glucose values rose on placebo (from 96.5 +/- 2.1 to 97.7 +/- 2.7 mg/dl) and on atenolol (from 99.7 +/- 2.2 to 102.1 +/- 4.8 mg/dl), but fell on propranolol (from 96.4 +/- 1.9 mg/dl to 87.2 +/- 2.5 mg/dl, p less than 0.01). These results indicate that blockade of vascular smooth muscle beta 2 receptors does not substantially alter hemodynamics during intense short-term exercise. Stimulation of renin release and lipolysis are produced through beta 1-adrenoceptor mechanisms, whereas beta 2 adrenoceptors are important in the provision of carbohydrate as an energy substrate for exercising muscle.
D000328:Adult; D001262:Atenolol / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood*; D005080:Exercise Test; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007773:Lactates / Q000097:blood; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood*; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D011897:Random Allocation; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012083:Renin / Q000097:blood*
D001786:Blood Glucose; D007773:Lactates; D011412:Propanolamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D011433:Propranolol; D012083:Renin; D009638:Norepinephrine; D004837:Epinephrine