PHARMACOLOGICAL STUDIES ON A NEW ANTIHYPERTENSIVE AGENT, S-2150, A BENZOTHIAZEPINE DERIVATIVE .3. HYPOTENSIVE AND ANTIMYOCARDIAL-STUNNING EFFECTS IN DOGS

The hypotensive and antimyocardial-stunning effects of a new 1,5-benzo thiazepine antihypertensive agent, S-2150, were investigated in dogs. S-2150 (30 mg/kg, p.o.) decreased the blood pressure in conscious rena l hypertensive dogs. Although the maximal hypotensive effect of S-2150 was observed at 5-9 h after administration, the effect of diltiazem w as seen at 2.0 h. Arrhythmia was not observed as a hypotensive effects of S-2150 but was markedly induced by diltiazem. In anesthetized open -chest dogs, S-2150 (20 mu g/kg/min, i.v.) caused a hypotensive effect similar to that of diltiazem but decreased myocardial work (double pr oduct) by much less than did diltiazem. S-2150 more promptly improved the local myocardial stunning caused by occlusion of the left anterior descending coronary artery and its reperfusion. This effect did not a ccompany the energy-sparing action in ischemic/reperfused myocardium, which was different from the case of diltiazem. In isolated dog mesent eric arteries, S-2150 relaxed KCI and phenylephrine contracture. These results suggest that S-2150 is a favorable hypotensive agent for hype rtensive patients with ischemic heart disease. Blockade of both Ca2+ c hannels and al-adrenoceptors by S-2150 seems to lead to cardiovascular effects different from those of diltiazem.