Using the telemetry system in spontaneously hypertensive rats (SHR), we evaluated the hemodynamic effects of four
adenosine analogs having different selectivity for A1 and A2a
adenosine receptor subtypes. The selective A2a agonists,
2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA) and 2-[4-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoaden osi ne (
CGS 21680), the selective A1 agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA) and the nonselective agonist, 5'-N-ethyl-carboxamidoadenosine (
NECA), were administered i.p. to conscious spontaneously hypertensive rats. For comparison, the
calcium channel blocker,
felodipine, was included. CCPA and 2HE-NECA were tested also by the oral route. Systolic and diastolic blood pressure and heart rate were recorded every 5 min for 24 hr after
drug administration. Data were analyzed using the curve fitting model recently elaborated. All compounds caused dose-dependent
antihypertensive effects. The i.p. dose inducing a decrease of 50 mm Hg (ED50) was calculated for both systolic and diastolic blood pressure. As regards diastolic blood pressure, ED50 values were: CCPA, 0.019 (0.013-0.027) mg/kg, 2HE-NECA, 0.009 (0.002-0.03) mg/kg,
CGS 21680, 0.155 (0.084-0.246) mg/kg,
NECA, 0.008 (0.004-0.016) mg/kg and
felodipine, 5.16 (4.18-7.18) mg/kg. At equiactive doses, the
antihypertensive effects of
adenosine agonists were shorter lasting [t1/2 for DBP were: CCPA, 54 (44-76) min, 2HE-NECA, 57 (46-71) min,
CGS 21680, 45 (21-94) min,
NECA, 61(38-97) min] than those of
felodipine [t1/2 = 233 (182-274) min]. After
oral administration (0.3, 1 and 3 mg/kg),
hypotension induced by 2HE-NECA was longer lasting than that of CCPA. 2HE-NECA,
CGS 21680 and
felodipine caused
tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)