Nitric oxide participates in the hypotensive effect induced by adenosine A2 subtype receptor stimulation.
In a previous study, we demonstrated that adenosine plays an important role in the central control of the cardiovascular system with involvement of adenosine A2 rather than A1 subtype receptors. In the present study, we investigated the putative relationship between nitric oxide (NO) and adenosine in the central and peripheral control of the cardiovascular system. Adult male normotensive anesthetized rats were treated with N6-cyclohexyladenosine (CHA), an A1-purinoceptor agonist, and 5'-N-cyclopropyl-carboxamidoadenosine (CPCA), an A2-purinoceptor agonist intracerebroventricularly (i.c.v. 3rd ventricle; 0.05-0.1-0.5 microgram/rat) and by intravenous injection (0.5-1-5 microgram kg-1 i.v.). CPCA and CHA induced a significant and dose-dependent decrease in arterial blood pressure (BP). CHA effects were less marked than CPA. Rats were pretreated with xanthine amine congener (XAC), and A1 adenosine antagonist, with 3,7-dimethyl-1-propargylxanthine (DMPX), an A2 adenosine antagonist (both administered at doses of 0.05 microgram/rat i.c.v. or 0.5 microgram kg-1 i.v.) and with N omega-nitro-L-arginine methyl ester, an NO synthase inhibitor, (L-NAME, 90 microgram/rat i.c.v. and 0.3 mg kg-1 i.v.). The intracerebroventricular and intravenous pretreatment with DMPX or L-NAME inhibited CPCA-induced hypotension; the effect of L-NAME was weaker than that of DMPX. The L-NAME inhibitory effect was reversed both in the central nervous system (CNS) and at the peripheral level by pretreatment with L-arginine (L-Arg; 90 mg kg-1 i.v.), a precursor of NO synthesis. Pretreatment with XAC, but not with L-NAME, reduced the hypotensive effect of CHA. Moreover, intracerebroventricular pretreatment with L-Arg (174 micrograms/rat) increased the hypotensive effect of CPCA.(ABSTRACT TRUNCATED AT 250 WORDS)
Stella
L
L
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, 2nd University of Naples, Italy.
Berrino
L
L
Filippelli
A
A
de Novellis
V
V
Rossi
F
F
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007022:Hypotension / Q000139:chemically induced; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D013805:Theobromine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D009569:Nitric Oxide; C027513:N(6)-cyclohexyladenosine; C024311:N-cyclopropyl adenosine-5'-carboxamide; C057837:3,7-dimethyl-1-propargylxanthine; D001120:Arginine; D000241:Adenosine; D013805:Theobromine; D019331:NG-Nitroarginine Methyl Ester