TY - JOUR
T1 - Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A(2A)-adenosine receptor agonists
AU - Alberti, C.
AU - Monopoli, A.
AU - Casati, C.
AU - Forlani, A.
AU - Sala, C.
AU - Nador, B.
AU - Ongini, E.
AU - Morganti, A.
PY - 1997
Y1 - 1997
N2 - Selective A(2A) adenosine receptor agonists are potent vasodilators that reduce blood pressure and induce marked increments in heart rate and plasma renin activity (PRA). To examine the mechanisms and pressor relevance of these cardiac and renin responses, we measured blood pressure and heart rate by telemetry and PRA in separate sets of spontaneously hypertensive rats (SHRs), which were given i.p. 2-hexynyl-5-methylcarboxamidoadenosine (2HE- NECA, 0.01 mg/kg) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N- ethylcarboxamidoadenosine (CGS 21680, 0.1 mg/kg) alone and after pretreatment with the β1-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 spirapril (3 mg/kg). Both A(2A) agonists induced marked reductions in blood pressure, associated with significant increments in heart rate and in PRA. Atenolol reduced blood pressure to the same extent as did the A(2A) agonists and markedly decreased heart rate and PRA. Pretreatment with atenolol entirely prevented the increase in heart rate and in PRA induced by the two A(2A) agonists but potentiated only slightly their antihypertensive effect. Spirapril alone reduced blood pressure and increased PRA and when given before 2HE-NECA potentiated its depressor and renin-stimulating effects by 44% and 69%, respectively. These results suggest that the increase in heart rate and in PRA induced by A(2A) agonists is the result of a reflex increase in sympathetic activity triggered by the decrease in blood pressure rather than of a direct stimulating effect on cardiac and renal A(2A)-adenosine receptors; the reactive activation of the renin-angiotensin system elicited by these compounds may contribute to blunting their antihypertensive effect.
AB - Selective A(2A) adenosine receptor agonists are potent vasodilators that reduce blood pressure and induce marked increments in heart rate and plasma renin activity (PRA). To examine the mechanisms and pressor relevance of these cardiac and renin responses, we measured blood pressure and heart rate by telemetry and PRA in separate sets of spontaneously hypertensive rats (SHRs), which were given i.p. 2-hexynyl-5-methylcarboxamidoadenosine (2HE- NECA, 0.01 mg/kg) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N- ethylcarboxamidoadenosine (CGS 21680, 0.1 mg/kg) alone and after pretreatment with the β1-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 spirapril (3 mg/kg). Both A(2A) agonists induced marked reductions in blood pressure, associated with significant increments in heart rate and in PRA. Atenolol reduced blood pressure to the same extent as did the A(2A) agonists and markedly decreased heart rate and PRA. Pretreatment with atenolol entirely prevented the increase in heart rate and in PRA induced by the two A(2A) agonists but potentiated only slightly their antihypertensive effect. Spirapril alone reduced blood pressure and increased PRA and when given before 2HE-NECA potentiated its depressor and renin-stimulating effects by 44% and 69%, respectively. These results suggest that the increase in heart rate and in PRA induced by A(2A) agonists is the result of a reflex increase in sympathetic activity triggered by the decrease in blood pressure rather than of a direct stimulating effect on cardiac and renal A(2A)-adenosine receptors; the reactive activation of the renin-angiotensin system elicited by these compounds may contribute to blunting their antihypertensive effect.
KW - β-Blockers
KW - A(2A)-adenosine agonists
KW - ACE inhibitors
KW - Plasma renin activity
KW - Spontaneously hypertensive rats
KW - Sympathetic nervous system
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U2 - 10.1097/00005344-199709000-00008
DO - 10.1097/00005344-199709000-00008
M3 - Article
C2 - 9300315
AN - SCOPUS:0031442356
VL - 30
SP - 320
EP - 324
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 3
ER -