Previous studies in our laboratory demonstrated that microcalorimetry is an appropriate method for estimating the physiological function of isolated rat brown adipocytes. In the present study, to elucidate the mode of action of typical and atypical beta-adrenoceptors on heat production of this cell, the effect of novel adrenergic beta 3-agonists was compared with that of other typical adrenergic reagents by direct microcalorimetry. Isoproterenol and beta 3-agonists, BRL37344, ICI215001, and CGP12177, increased heat production in a dose-dependent manner, however, phenylephrine had no effect. Propranolol and pindolol did not increase the heat production but attenuated the effect of isoproterenol and BRL37344 in a dose-dependent manner. Molar IC50 values of propranolol and pindolol for BRL37344 were about 10(-5) and 3 x 10(-6) M, respectively, whereas those of the two antagonists for isoproterenol were about 3 x 10(-7)M. The pA2 values by Schild analysis of propranolol vs. isoproterenol and BRL37344 were 7.91 and 6.13, respectively. These results suggest that heat production may be regulated via both beta 3- and typical beta-adrenoceptors in brown adipocytes.

During sympathetic nerve stimulation, the vasoconstrictive actions of NPY are masked by norepinephrine under intact alpha-adrenoceptor conditions, manifest during alpha-blockade and modulated by KATP channel activity.

We examined humoral and/or locally produced vasoactive factors involved in modulating sympathetic coronary vasoconstriction via the ATP-sensitive K (KATP) channel in 42 anesthetized dogs. Glibenclamide (30 micrograms.kg-1.min-1 ic or 0.6 mg.kg-1.min-1 left atrial injection) augmented coronary vascular resistance (CVR) at baseline and during cardiac sympathetic nerve stimulation (2-20 Hz), with a greater increase seen in the subepicardial region than in the subendocardial region both during beta-adrenergic receptor blockade and alpha- and beta-receptor blockade [P < 0.05 and P < 0.05 (n = 6 and 18 dogs), analysis of variance]. In contrast, pinacidil (10 micrograms.kg-1.min-1; n = 8 dogs) suppressed CVR. Glibenclamide enhanced CVR response to locally administered norepinephrine of 0.001-0.1 microgram.kg-1.min-1 (P < 0.05, analysis of covariance; n = 5 dogs) but did not enhance norepinephrine or neuropeptide Y overflow (n = 18 dogs). CVR was not modified by calcitonin gene-related peptide (CGRP) antagonist [CGRP-(8-37)], 8-phenyltheophylline, or N omega-nitro-L-arginine (n = 11 dogs). Thus sympathetic coronary vasoconstriction is modified by coronary vascular KATP channels with a transmural difference. However, CGRP, adenosine, and endothelial nitric oxide production are not involved in the modulation.

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