Document Detail

Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists.
MedLine Citation:
PMID:  9300315     Owner:  NLM     Status:  MEDLINE    
Selective A2A 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-ethylcarboxamidoadenosin e (CGS 21680, 0.1 mg/kg) alone and after pretreatment 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 spirapril (3 mg/kg). Both A2A 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 A2A 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 A2A 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 A2A 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 A2A-adenosine receptors; the reactive activation of the renin-angiotensin system elicited by these compounds may contribute to blunting their antihypertensive effect.
C Alberti; A Monopoli; C Casati; A Forlani; C Sala; B Nador; E Ongini; A Morganti
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  30     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-10-20     Completed Date:  1997-10-20     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  320-4     Citation Subset:  IM    
Istituto di Clinica Medica e Terapia Medica, Universitá e Ospedale Maggiore (IRCCS), Milan, Italy.
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MeSH Terms
Adenosine / analogs & derivatives*,  pharmacology
Adenosine-5'-(N-ethylcarboxamide)* / analogs & derivatives*
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Antihypertensive Agents / pharmacology*
Blood Pressure / drug effects*
Heart Rate / drug effects*
Injections, Intraperitoneal
Phenethylamines / pharmacology*
Platelet Aggregation Inhibitors / pharmacology*
Rats, Inbred SHR
Receptors, Purinergic P1 / agonists*
Renin / blood,  drug effects*
Renin-Angiotensin System / drug effects*
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Phenethylamines; 0/Platelet Aggregation Inhibitors; 0/Receptors, Purinergic P1; 120225-54-9/CGS 21680; 141018-30-6/2-hexynyladenosine-5'-N-ethylcarboxamide; 35920-39-9/Adenosine-5'-(N-ethylcarboxamide); 58-61-7/Adenosine; EC

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