SR 33557 (SR) is a new calcium channel blocker belonging to the chemical class of indolizinsulfones (IC50 = 0.6 nM, 3H-nitrendipine). Its hypotensive effects were studied in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, and compared to those of Nitrendipine (Nit) (IC50 = 0.8 nM, 3H-nitrendipine). SR was given intravenously (IV) at 0.3, 1 and 3 mg/kg (n = 4 to 6) and orally (PO) at 3, 10, 30 and 60 mg/kg (n = 4 to 7). Nitrendipine was studied at 0.3 mg/kg (IV) and 10 mg/kg (PO). Blood pressure (BP) and heart rate (HR) were measured for 120 min, and for 24 h at 30 mg/kg. The IV injection of SR induced an immediate and dose-dependent decrease in BP. The maximal diastolic hypotension was situated between 11 p. 100 at 0.3 mg/kg and 45 p. 100 at 3 mg/kg (basal values: 133 +/- 6 and 131 +/- 5 mmHg). These effects lasted between 30 min and over 2 hours. The oral administration of SR induced a dose-dependent fall in BP at 3 mg/kg and upwards. The maximal diastolic hypotension appeared within 60 and 120 min and were situated between 8 p. 100 at 3 mg/kg and 28 p. 100 at 60 mg/kg (basal values: 130 +/- 7 and 133 +/- 2 mmHg). At 30 mg/kg, the hypotension lasted for 8 hours. SR was roughly 10 times less hypotensive in WKY than in SHR. HR did not change.(ABSTRACT TRUNCATED AT 250 WORDS)