Differentiation of hemodynamic, humoral and metabolic responses to beta 1- and beta 2-adrenergic stimulation in man using atenolol and propranolol.

Abstract

SUMMARY The respective contributions of 3-adrenoceptor subtypes to the hemodynamic, humoral and metabolic consequences of adrenergic stimulation during graded exercise in man were investigated using nonselective 8-adrenoceptor blockade with propranolol and ,81-adrenoceptor blockade with atenolol. Doses of these agents that produced comparable suppression of 1,1 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/di) 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 < 0.01). These results indicate that blockade of vascular smooth muscle 12 receptors does not substantially alter hemodynamics during intense short-term exercise. Stimulation of renin release and lipolysis are produced through /83-adrenoceptor mechanisms, whereas /2 adrenoceptors are important in the provision of carbohydrate as an energy substrate for exercising muscle.

Beta 1‐selective and non‐selective beta‐adrenoceptor blockade, anaerobic threshold and respiratory gas exchange during exercise.

“…These effects have been noted before by us, and are very much larger during more intense or more prolonged exercise (McLeod et al, 1983; Atenolol concentrations ranged from 186 to 748 ng/ml; total propranolol concentrations were between 5 and 33 ng/ml. In previous studies, similar concentrations of atenolol and propranolol were obtained.…”

“…In previous studies, similar concentrations of atenolol and propranolol were obtained. 31-adrenoceptor blockade as assessed by reduction in exercise heart rates was almost identical for the non-selective and ,B1-selective adrenoceptor antagonists (McLeod et al, 1983;. In the present investigation, atenolol was somewhat more potent as a ,I-adrenoceptor antagonist as assessed by effect on exercise heart rate.…”

“…In the present study, neither propranolol nor atenolol modified oxygen consumption or carbon dioxide production. Our previous investigations however have strongly suggested that propranolol but not atenolol impairs hepatic glucose release (McLeod et al, 1983(McLeod et al, , 1984 (Felig & Wahren, 1975). There is evidence for enhanced intramuscular glycogenolysis during exercise after propranolol which would support this concept (Juhlin-Dannfelt et al, 1982).…”

Cardiovascular and Metabolic Alterations in Mice Lacking Both β1- and β2-Adrenergic Receptors

“…It is interesting to note that the metabolic alteration seen in ␤1-/␤2-AR double knockouts appears to result from combined ␤1-and ␤2-AR deficiency, as neither single ␤1-nor ␤2-AR knockouts display the same degree of metabolic hypo-responsiveness during exercise. In humans, such metabolic responses were traditionally thought to be regulated primarily by the ␤2-AR (31), although there are instances where both ␤1-and ␤2-ARs appear to be involved in the metabolic response to exercise (37,38). Our results in mice suggest that both the ␤1-and ␤2-AR normally subserve redundant metabolic functions in vivo and that both receptor subtypes must be eliminated before significant defects are manifested.…”

The assessment of the beta‐adrenoceptor blocking activity and cardioselectivity of Koe 3290 in normal subjects.

“…In man, studies have shown that this response is mediated by a P2-adrenoceptor effect (Goldberg et al, 1975;William-Olsson et al, 1979) but in other studies with exercise stimulation the importance of the P1-adrenoceptor mediated response (Laustola et al, 1983;McLeod et al, 1983) is apparent.…”