The hemodynamic responses to 5'-N-ethylcarboxamide
adenosine (
NECA), a nonselective
adenosine agonist, were compared to those elicited by the
sodium salt of 2-[
p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido
adenosine (CGS 21680C) and N6-2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl
adenosine (
CGS 24012), two structurally dissimilar selective A2 agonists in conscious spontaneously hypertensive rats (SHR). Dose-related reductions in mean arterial pressure occurred after bolus administration of
NECA, CGS 21680C and
CGS 24012. Dose-dependent
tachycardia was seen with both CGS 21680C and
CGS 24012, whereas
NECA produced a biphasic response on heart rate. At high doses (3 and 10 micrograms/kg),
NECA evoked an immediate and dramatic fall in heart rate, followed by a more gradual and long-lasting
tachycardia. At equihypotensive doses, both CGS 21680C and
CGS 24012 produced significant increases in cardiac output, but
NECA had no effect. Although each of the
adenosine agonists reduced total peripheral resistance, the greatest change was produced by CGS 21680C. Hindquarter, renal and mesenteric vascular resistances were significantly reduced by both CGS 21680C and
CGS 24012, whereas only mesenteric vascular resistance was reduced with
NECA.
CGS 24012 reduced renal vascular resistance to the greatest extent and produced a concomitant significant increase in renal blood flow. Marked elevation in plasma
renin activity occurred with
CGS 24012 and CGS 21680C, whereas no change was seen after
NECA. The hemodynamic responses to
NECA, CGS 21680C and
CGS 24012 were significantly reduced by the
adenosine antagonist, 8-(p-sulfophenyl)
theophylline, suggesting that these agents act through stimulation of
adenosine receptors in the conscious SHR. Furthermore, blockade of the
beta adrenergic receptor with
metoprolol (1 mg/kg, i.v.) significantly attenuated the increase in heart rate produced by
NECA, CGS 21680C and
CGS 24012. The cardiovascular pattern of responses to the two selective A2 agonists, CGS 21680C and
CGS 24012, are distinct from those of
NECA, the nonselective
adenosine agonist. The responses to both CGS 21680C and
CGS 24012 indicate that systemic vasodilation, with resultant cardioexcitation and stimulation of
renin release, are the predominant hemodynamic effects of selective A2 agonists in the conscious SHR. In contrast, the cardiovascular effects produced by
NECA are mediated by activation of both A1 and A2 receptors.