Increased myocardial oxygen consumption and resting heat production, as measured by microcalorimetry, after propranolol and carvedilol treatment: Is there a partial agonistic effect in the rat?

Abstract

This study investigated the influence of β-blockade on the resting heat production of myocardial tissue by microcalorimetry. During one week, propranolol (β1β2-adrenoceptor antagonist) was orally given to 14 rats − 5 mg kg−1 once daily, and carvedilol (β1β2- and α1-antagonist) to eight rats − 3 mg kg−1 once daily; 36 rats were controls. Thin slices of cardiac tissue, ≈10 mg, were removed from the apex. Carbogen-saturated Krebs-Ringer bicarbonate buffer with glucose as substrate was pumped through the microcalorimetric ampoule during the measurement at 37°C. Unexpectedly, the mean resting heat production was higher after both propranolol, 1.25 mW g−1 wet tissue (p < 0.01, ANOVA) and carvedilol, 1.19 mW g−1 (p < 0.05) treatments, than in the control group, 1.01 mW g−1. The same applied to oxygen consumption. The calculated anaerobic fractions were 16, 8 and 24% in the respective groups, but differences were not significant. Also, when added in vitro, propranolol caused an enhanced myocardial resting heat production by an average of 23%. As resting myocardial metabolism contributes to the overall cardiac energetics to a relatively minor extent, the net result of treatment will probably be of only marginal physiological importance. The experimental outcome is indicative of a stimulation of resting myocardial metabolic activity after propranolol and carvedilol, rather than a predicted decrease. We hypothesize that the absence of anything to depress in the non-beating heart tissue, reveals a small degree of partial β-agonist activity, possibly via the newly discovered β3-adrenoceptor.