Vasodilator effects of LF 2.0254, a new 1,4-dihydropyridine. Comparison with nifedipine

LF 2.0254 is a new 1.4 dihydropyridine that relaxes vascular smooth muscles by blockade of calcium entry mediated by depolarisation. In rabbit aortas contracted by KCl (15 to 55 mM) or CaCl2 (2 mM), LF 2.0254 differs markedly from nifedipine and nicardipine because of its slow onset of action, the inhibitory effect increasing with the duration of tissular contact. LF 2.0254 has only slight negative chronotropic and inotropic effects on isolated guinea-pig atria as well as in anesthetized dogs after intravenous administration. Furthermore, in open-chest anesthetized dogs, LF 2.0254 decreases mean arterial blood pressure and since cardiac output is maintained total peripheral resistance is decreased. LF 2.0254 administered orally to perinephritic hypertensive dogs (0.1 and 0.3 mg/kg) and to spontaneously hypertensive rats (0.3 to 10 mg/kg) induces a more pronounced and long-lasting hypotensive action than nifedipine. In conclusion, these results suggest that LF 2.0254 could be useful in the treatment of hypertension associated or not with cardiac insufficiency.