MECHANISM AND PRESSOR RELEVANCE OF THE SHORT-TERM CARDIOVASCULAR AND RENIN EXCITATORY ACTIONS OF THE SELECTIVE A(2A)-ADENOSINE RECEPTOR AGONISTS

Selective A(2A) adenosine receptor agonists are potent vasodilators th at reduce blood pressure and induce marked increments in heart rate an d plasma renin activity (PRA). To examine the mechanisms and presser r elevance of these cardiac and renin responses, we measured blood press ure and heart rate by telemetry and PRA in separate sets of spontaneou sly hypertensive rats (SHRs), which were given i.p. 2-hexynyl-5-methyl carboxamidoadenosine (2HE-NECA, 0.01 mg/kg) and hyl)phenethylamino]-5' -N-ethylcarboxamidoadenosine (CGS 21680, 0.1 mg/kg) alone and after pr etreatment with the beta(1)-adrenoceptor blocking agent atenolol (100 mg/kg). The effects of 2HE-NECA (0.003 mg/kg) also were examined after pretreatment with the angiotensin-converting enzyme (ACE) inhibitor s pirapril (3 mg/kg). Both A(2A) agonists induced marked reductions in b lood pressure, associated with significant increments in heart rate an d in PRA. Atenolol reduced blood pressure to the same extent as did th e A(2A) agonists and markedly decreased heart rate and PRA. Pretreatme nt with atenolol entirely prevented the increase in heart rate and in PRA induced by the two A(2A) agonists but potentiated only slightly th eir antihypertensive effect. Spirapril alone reduced blood pressure an d increased PRA and when given before 2HE-NECA potentiated its depress or and renin-stimulating effects by 44% and 69%, respectively. These r esults suggest that the increase in heart rate and in PRA induced by A (2A) agonists is the result of a reflex increase in sympathetic activi ty triggered by the decrease in blood pressure rather than of a direct stimulating effect on cardiac and renal A(2A)-adenosine receptors, th e reactive activation of the renin-angiotensin system elicited by thes e compounds may contribute to blunting their antihypertensive effect.