title: Constant-pressure perfusion of rat hindlimb shows alpha- and beta-adrenergic stimulation of oxygen consumption.
abstract: Isolated rat hindlimbs were perfused at 37 degrees C and constant physiological pressure (80 +/- 0.5 mmHg) while the flow rate that was allowed to freely self-adjust was monitored. Under these conditions, evidence was obtained for both alpha- and beta-adrenergic stimulation of oxygen consumption (VO2) in contrast to constant-flow perfusion, which has only convincingly shown alpha-adrenergic stimulation of VO2 in response to adrenergic agents. Addition of norepinephrine (NE; 1-33 nM) led to an increase in VO2 with a maximum of 29% above the basal value at 3.3 nM, even though the flow rate decreased. Phenylephrine (3.3-33 nM) and vasopressin (10-100 pM) also showed similar, but lesser in magnitude, vasoconstriction-associated stimulatory effects on VO2. Prazosin (an alpha 1-antagonist) completely reversed the NE-mediated decrease in flow rate and significantly blocked the increased VO2. In contrast, isoproterenol (10-1,000 nM) increased both flow rate (30%) and VO2 (32%). The isoproterenol-stimulated VO2 was not blocked by the beta 1-, beta 2-antagonist propranolol (10 microM), although the increased flow was reversed. In the presence of propranolol (1 or 10 microM), BRL-35135A (a beta 3-agonist) also stimulated VO2 (18%) without significant change in flow rate. These results lend further support to the role of the alpha 1-adrenoceptor in muscle VO2. In addition there is evidence for the presence of a functional beta 3-adrenoceptor as an additional subtype responsible for NE-mediated thermogenesis in the rat hindlimb.
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010477:Perfusion / Q000379:methods; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018663:Adrenergic Agents; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007773:Lactates; D019344:Lactic Acid