adenosine-5--(n-ethylcarboxamide) and Hypotension

1. Adenosine produced a biphasic lowering of the mean BP with a drastic bradycardic effect at the highest doses. The first phase hypotensive response was significantly reduced by the nitric oxide (NO) synthase inhibitor L-NAME. 2. The A(2a)/A(2b) agonist NECA produced hypotensive and bradycardic responses similar to those elicited by adenosine, which were not significantly modified by the A(2b) antagonist enprofylline. 3. The A(2a) agonist CGS 21680 did not significantly influence basal HR while induced a hypotensive response antagonized by the A(2a) selective antagonist ZM 241385, and reduced by both L-NAME and the guanylate cyclase inhibitor methylene blue. 4. The A(1) agonist R-PIA showed a dose-dependent decrease in BP with a drastic decrease in HR at the highest doses. The A(1) selective antagonist DPCPX significantly reduced the bradycardic activity and also the hypotensive responses obtained with the lowest doses while it increased those obtained with the highest ones. 5. The A(1)/A(3) agonist APNEA, in the presence of the xanthinic non-selective antagonist 8-pSPT, maintained a significant hypotensive, but not bradycardic, activity, not abolished by the histamine antagonist diphenhydramine. 6. The selective A(3) agonist IB-MECA revealed a weak hypotensive and bradycardic effect, but only at the highest doses. 7. In conclusion, in the systemic cardiovascular response to adenosine two major components may be relevant: an A(2a)- and NO-mediated hypotension, and a bradycardic effect with a consequent hypotension, via atypical A(1) receptors. Finally, an 8-pSPT-resistant hypotensive response not attributable to A(3) receptor-stimulation or to release of histamine by mastocytes or other immune cells was observed.

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Animals; Blood Pressure; Diphenhydramine; Dose-Response Relationship, Drug; Enzyme Inhibitors; Guinea Pigs; Heart Rate; Hypotension; Male; Methylene Blue; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Phenethylamines; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Receptors, Purinergic P1; Theophylline; Triazines; Triazoles; Vasodilator Agents; Xanthines

A lectin, which exerted a hypotensive action in rats after intravenous injection via the jugular vein, was isolated from the mycelia of the edible mushroom Tricholoma mongolicum. The lectin possessed a molecular weight of 37 K and its hypotensive activity was dose-dependent. Administration of the lectin at a dose of 10 mg/kg body weight caused a mean arterial blood pressure reduction of 95.3 +/- 7.4 mmHg. The lectin's hypotensive action was not mediated via autonomic ganglion transmission, alpha-adrenoceptors, beta-adrenoceptors, cholinergic receptors, histaminergic receptors, nor the renin-angiotensin system, but it was probably mediated through vasorelaxation via adenosine A2 receptors and/or nitric oxide production.

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Adrenergic alpha-Agonists; Animals; Aorta; Basidiomycota; Dose-Response Relationship, Drug; Heart; Heart Atria; Hemagglutination Tests; Hypotension; Lectins; Male; Methoxamine; Muscle, Smooth, Vascular; Myocardial Contraction; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P1; Vasodilation

The cardiovascular effects of N6-2-(4-aminophenyl)ethyladenosine (APNEA), which when radiolabelled with 125I shows high affinity for the newly described adenosine A3 receptor, have been investigated in the angiotensin II-supported circulation of the pithed rat. APNEA induces hypotensive responses which are unaffected by high doses (20-40 mg kg-1) of the broad spectrum, adenosine receptor antagonist, 8-(p-sulphophenyl)theophylline (8-SPT). 8-SPT-resistant falls in blood pressure are also seen, in the absence of bradycardia, with 5'-N-ethylcarboxamidoadenosine (NECA) and the R- and S-enantiomers of N6-phenylisopropyladenosine (PIA). Xanthine insensitivity, high potencies of APNEA, NECA and R-PIA, and an enantiomeric selectivity favouring R- over S-PIA are distinguishing features of the adenosine A3 receptor. We suggest that hypotension in the pithed rat may be a functional correlate of this site.

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Angiotensin II; Animals; Blood Pressure; Decerebrate State; Dose-Response Relationship, Drug; Hypotension; Male; Phenylisopropyladenosine; Rats; Rats, Sprague-Dawley; Receptors, Purinergic; Stereoisomerism; Vasodilator Agents

This study investigated the potential role of adenosine in cerebral blood flow (CBF) regulation in the neonate during moderate and severe hypotension. Experiments were done in anesthetized, 1- to 3-day-old piglets. Regional CBF (determined by radiolabeled microsphere technique) and cerebral metabolic rate for O2 (CMRO2) were measured (a) during normotension and (b) during a 3-min period of moderate (58 +/- 9 mm Hg) or severe (36 +/- 7 mm Hg) hypotension produced by the inflation of a balloon catheter placed in the aortic root. Measurements of CBF and CMRO2 were performed successively after intracerebroventricular (i.c.v.) injections of vehicle (n = 17), the adenosine receptor blocker 8-phenyltheophylline (8-PT, 10 micrograms, n = 14), and the A2-receptor agonist 5'-N-(ethylcarboxamide)adenosine (NECA, 2 ng, n = 8). After i.c.v. administration of vehicle, none of the parameters studied was significantly altered by moderate hypotension, but severe hypotension decreased the total CBF (mean +/- SD) from 86 +/- 24 to 40 +/- 15 ml min-1 100 g-1 and CMRO2 from 3.2 +/- 0.8 to 1.8 +/- 1.0 ml min-1 100 g-1 (p less than 0.05). Administration of 8-PT did not alter these parameters during normotension, but significantly decreased CBF during moderate hypotension compared to postvehicle values (53 +/- 11 versus 81 +/- 12 ml min-1 100 g-1, p less than 0.05). This loss of autoregulation was completely reversed by NECA. During severe hypotension, 8-PT altered the CBF redistribution towards the brainstem.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Animals; Animals, Newborn; Blood Flow Velocity; Brain; Cerebrovascular Circulation; Hypotension; Hypoxanthine; Hypoxanthines; Inosine; Oxygen; Receptors, Purinergic; Swine; Theophylline; Vascular Resistance