Involvement of β‐adrenoceptors in the cardiovascular responses induced by selective adenosine A(2A) and A(2B) receptor agonists

A(2A) and A(2B) adenosine receptors produce regionally selective regulation of vascular tone and elicit differing effects on mean arterial pressure (MAP), whilst inducing tachycardia. The tachycardia induced by the stimulation of A(2A) or A(2B) receptors has been suggested to be mediated by a reflex increase in sympathetic activity. Here, we have investigated the role of β(1)‐ and β(2)‐adrenoceptors in mediating the different cardiovascular responses to selective A(2A) and A(2B) receptor stimulation. Hemodynamic variables were measured in conscious male Sprague‐Dawley rats (350–450 g) via pulsed Doppler flowmetry. The effect of intravenous infusion (3 min per dose) of the A(2A)‐selective agonist CGS 21680 (0.1, 0.3, 1.0 µg.kg(−1).min(−1)) or the A(2B)‐selective agonist BAY 60–6583 (4.0, 13.3, 40.0 µg.kg(−1).min(−1)) in the absence or following pre‐treatment with the non‐selective β‐antagonist propranolol (1.0 mg.kg(−1)), the selective β(1)‐antagonist CGP 20712A (200 µg.kg(−1)), or the selective β(2)‐antagonist ICI 118,551 (2.0 mg.kg(−1)) was investigated (maintenance doses also administered). CGP 20712A and propranolol significantly reduced the tachycardic response to CGS 21680, with no change in the effect on MAP. ICI 118,551 increased BAY 60–6583‐mediated renal and mesenteric flows, but did not affect the heart rate response. CGP 20712A attenuated the BAY 60–6583‐induced tachycardia. These data imply a direct stimulation of the sympathetic activity via cardiac β(1)‐adrenoceptors as a mechanism for the A(2A)‐ and A(2B)‐induced tachycardia. However, the regionally selective effects of A(2B) agonists on vascular conductance were independent of sympathetic activity and may be exploitable for the treatment of acute kidney injury and mesenteric ischemia.