Adenosine strongly potentiates pressor responses to nicotine in rats.
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Intravenous infusion of subhypotensive doses of adenosine strongly potentiates the pressor response of anesthetized rats to nicotine. A dose of nicotine (40 micrograms/kg, i.v.), which, given alone, elicits a peak increase in diastolic pressure of approximately equal to 15 mm Hg, increases pressure by approximately equal to 70 mm Hg when arterial plasma adenosine levels have been increased to 2 microM from a basal concentration of approximately equal to 1 microM. The pressor response to cigarette smoke applied to the lungs is also strongly potentiated during infusion of adenosine. Slightly higher adenosine concentrations (approximately equal to 4 microM) attenuate pressor responses to electrical stimulation of preganglionic sympathetic nerves, or to injections of the alpha-adrenergic agonist phenylephrine, but continue to potentiate pressor responses to nicotine. Low doses (0.25-5 micrograms/kg) of the synthetic adenosine receptor agonists 5'-N-cyclopropylcarboxamidoadenosine, 2-chloroadenosine, and N6-L-phenylisopropyladenosine also potentiate pressor responses to nicotine. Caffeine and theophylline (10 mg/kg) block the potentiating effect of adenosine, and also decrease basal responses to nicotine, suggesting that endogenous adenosine might normally potentiate some nicotine responses. The synergism between nicotine and adenosine appears to take place within sympathetic ganglia.