Pharmacological studies on a new antihypertensive agent, S-2150, a benzothiazepine derivative: 3. Hypotensive and antimyocardial-stunning effects in dogs

J Cardiovasc Pharmacol. 1997 Feb;29(2):180-7. doi: 10.1097/00005344-199702000-00005.

Abstract

The hypotensive and antimyocardial-stunning effects of a new 1,5-benzothiazepine antihypertensive agent, S-2150, were investigated in dogs. S-2150 (30 mg/kg, p.o.) decreased the blood pressure in conscious renal hypertensive dogs. Although the maximal hypotensive effect of S-2150 was observed at 5-9 h after administration, the effect of diltiazem was 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 micrograms/kg/min, i.v.) caused by hypotensive effect similar to that of diltiazem but decreased myocardial work (double product) 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 accompany the energy-sparing action in ischemic/reperfused myocardium, which was different from the case of diltiazem. In isolated dog mesenteric arteries, S-2150 relaxed KCl and phenylephrine contracture. These results suggest that S-2150 is a favorable hypotensive agent for hypertensive patients with ischemic heart disease. Blockage of both Ca2+ channels and alpha 1-adrenoceptors by S-2150 seems to lead to cardiovascular effects different from those of diltiazem.

MeSH terms

  • Adenosine Triphosphate / analysis
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Coronary Disease / metabolism
  • Diltiazem / analogs & derivatives*
  • Diltiazem / pharmacology
  • Dogs
  • Hemodynamics / drug effects
  • Hypertension, Renal / drug therapy
  • In Vitro Techniques
  • Male
  • Myocardial Stunning / prevention & control*
  • Vasodilation / drug effects

Substances

  • Antihypertensive Agents
  • S 2150
  • Adenosine Triphosphate
  • Diltiazem