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

• Published in: Journal of cardiovascular pharmacology Vol. 29; no. 2; p. 180
• Main Authors: Kimoto, S, Haruna, M, Matsuura, E, Uno, O, Ishii, M, Hirono, S, Yoshimura, K, Ueda, M, Iwaki, K
• Format: Journal Article
• Language: English
• Published: United States 01.02.1997
• Subjects: 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
• ISSN: 0160-2446
• DOI: 10.1097/00005344-199702000-00005

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.