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-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.
Kimoto
S
S
Developmental Research Laboratories, Shionogi & Co., Ltd., Shiga, Japan.
Haruna
M
M
Matsuura
E
E
Uno
O
O
Ishii
M
M
Hirono
S
S
Yoshimura
K
K
Ueda
M
M
Iwaki
K
K
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003327:Coronary Disease / Q000378:metabolism; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006977:Hypertension, Renal / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D017682:Myocardial Stunning / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; C104615:S 2150; D000255:Adenosine Triphosphate; D004110:Diltiazem