NTS A2a purinoceptor activation elicits hindlimb vasodilation primarily via a b-adrenergic mechanism

Kitchen, Amy M., Tadeusz J. Scislo, and Donal S. O’Leary. NTS A2a purinoceptor activation elicits hindlimb vasodilation primarily via a b-adrenergic mechanism. Am J Physiol Heart Circ Physiol 278: H1775–H1782, 2000.— Previously, we have shown that activation of adenosine A2a receptors in the subpostremal nucleus tractus solitarii (NTS) via microinjection of the selective A2a receptor agonist CGS21680 elicits potent, dose-dependent decreases in mean arterial pressure and preferential, marked hindlimb vasodilation. Although A2a receptor activation does not change lumbar sympathetic nerve activity, it does markedly enhance the preganglionic adrenal sympathetic nerve activity, which will increase epinephrine release and could subsequently elicit hindlimb vasodilation via activation of b2-adrenergic receptors. Therefore we investigated whether this hindlimb vasodilation was due to neural or humoral mechanisms. In chloralose-urethan-anesthetized male Sprague-Dawley rats, we monitored cardiovascular responses to stimulation of NTS adenosine A2a receptors (CGS-21680, 20 pmol/50 nl) in the intact control animals; after pretreatment with propranolol (2 mg/kg iv), a b-adrenergic antagonist; after bilateral lumbar sympathectomy; after bilateral adrenalectomy; and after combined bilateral lumbar sympathectomy and adrenalectomy. After b-adrenergic blockade, stimulation of NTS adenosine A2a receptors produced a pressor response and a hindlimb vasoconstriction. Lumbar sympathectomy reduced the vasodilation seen in the intact animals by ,40%, and adrenalectomy reduced it by ,80%. The combined sympathectomy and adrenalectomy virtually abolished the hindlimb vasodilation evoked by NTS A2a receptor activation. We conclude that the preferential, marked hindlimb vasodilation produced by stimulation of NTS adenosine A2a receptors is mediated by both the efferent sympathetic nerves directed to the hindlimb and the adrenal glands via primarily a b-adrenergic mechanism.