Alpha 2-adrenoceptor stimulation can augment coronary vasodilation maximally induced by adenosine in dogs

Abstract

To determine whether alpha 2-adrenoceptor stimulation can augment adenosine-induced coronary vasodilation, 34 open-chest dogs were studied. When a small dose of clonidine (up to 0.24 micrograms.kg-1.min-1 ic) was administered under beta-adrenoceptor blockade, coronary blood flow [312 +/- 16 (SE) ml.100 g-1.min-1] maximally induced by intracoronary infusion of adenosine was further increased (P less than 0.05) by 66 +/- 16 ml.100 g-1.min-1, despite no significant changes in coronary perfusion pressure, myocardial oxygen consumption, and coronary venous adenosine concentration. However, when a larger dose of clonidine (0.36-0.60 micrograms.kg-1.min-1) was infused, adenosine-induced flow progressively decreased. This biphasic action of the alpha 2-adrenoceptor activity was also observed when the dose of norepinephrine was increased during alpha 1-adrenoceptor blockade with prazosin. Norepinephrine up to 0.24 micrograms.kg-1.min-1 (ic) further increased adenosine-induced coronary blood flow by 24 +/- 5% (P less than 0.001), whereas hyperemic flow was decreased by a larger dose of norepinephrine. In contrast to the alpha 2-adrenoceptor stimulation, the alpha 1-adrenoceptor stimulation (norepinephrine with yohimbine) progressively decreased coronary blood flow. Furthermore, with a small dose of clonidine, reactive hyperemic flow significantly increased compared with that without clonidine (303 +/- 13 vs. 355 +/- 13 ml.100 g-1.min-1, P less than 0.001), but a larger dose of clonidine adversely reduced reactive flow (254 +/- 18 ml.100 g-1.min-1, P less than 0.001). Adenosine release during reactive hyperemia with and without intracoronary infusions of clonidine were not altered significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine and Cardioprotection in the Diseased Heart

“…[59][60][61] This is consistent with the earlier studies of Nayler et al 63 They observed that phenoxybenzamine, a non-specific -adrenoceptor antagonist, blocks the vasodilatory action of adenosine in isolated rat and guinea pig hearts. [60][61][62] Furthermore, the reduction in ischemiainduced myocardial damage by administration of clonidine in coronary hypoperfusion and in coronary microembolization strongly suggests that adenosine plays an important role in the dilation of the coronary arterial bed; clonidine significantly increased coronary blood flow in both of the ischemic models without augmentation of adenosine release. 63 In summary, during ischemia, coronary blood flow is regulated by metabolic and neural mechanisms, ie, adenosine-induced coronary vasodilation and -adrenoceptormediated vasoconstriction.…”

“…The underlying mechanism for this phenomenon may be different from that of adenosine release when -adrenoceptors are stimulated. 59 We have also found that 2-adrenergic activity modifies the vasodilatory action of adenosine (Fig 3); a low dose of the 2-adrenoceptor agonist clonidine enhances adenosineinduced coronary vasodilation, [60][61][62] and low doses of yohimbine and rauwolscine, 2-adrenoceptor antagonists, reduce the coronary flow response to either endogenous or exogenous adenosine. [59][60][61] This is consistent with the earlier studies of Nayler et al 63 They observed that phenoxybenzamine, a non-specific -adrenoceptor antagonist, blocks the vasodilatory action of adenosine in isolated rat and guinea pig hearts.…”

“…59 We have also found that 2-adrenergic activity modifies the vasodilatory action of adenosine (Fig 3); a low dose of the 2-adrenoceptor agonist clonidine enhances adenosineinduced coronary vasodilation, [60][61][62] and low doses of yohimbine and rauwolscine, 2-adrenoceptor antagonists, reduce the coronary flow response to either endogenous or exogenous adenosine. [59][60][61] This is consistent with the earlier studies of Nayler et al 63 They observed that phenoxybenzamine, a non-specific -adrenoceptor antagonist, blocks the vasodilatory action of adenosine in isolated rat and guinea pig hearts. [60][61][62] Furthermore, the reduction in ischemiainduced myocardial damage by administration of clonidine in coronary hypoperfusion and in coronary microembolization strongly suggests that adenosine plays an important role in the dilation of the coronary arterial bed; clonidine significantly increased coronary blood flow in both of the ischemic models without augmentation of adenosine release.…”

Adrenergic blockade blunts adenosine concentration and coronary vasodilation during hypoxia.

“…31,32 The mechanism for the adrenergic-adenosine interaction found in the present experiments is unknown. Adrenergic 3-receptor agonists have been shown to increase adenosine concentration in both coronary venous plasma33.34 and epicardial well'2 measurements.…”

Heterogeneity of Coronary Flow Reserve in the Examination of Multiple Individual Allograft Coronary Arteries

“…30 In animal models, the distribution of adrenergic receptors, in particular ␣ 2 -receptors, across the microcirculation is heterogeneous 31 and may explain enhanced vasoreactivity in response to adenosine. 32,33 Because reinnervation is heterogeneous, the minimal achievable coronary vascular resistance in innervated versus denervated beds may be different. Reinnervation differences could potentially modify regional left ventricular metabolism and subsequently regional blood flow.…”