Participation of angiotensin II and bradykinin in contractile function in dog stunned myocardium.
We examined the effects of enalapril and 4'-[(1, 4'-dimethyl-2'-propyl-[2,6'-bi-1H-enzimidazole]-1'-yl)methyl]-[1, 1'-biphenyl]-2-carboxylic acid (BIBR-277), an angiotensin II receptor antagonist, on contractile dysfunction in the stunned myocardium. Dogs were subjected to 20-min ligation of the coronary artery, followed by 60-min reperfusion. Saline, enalapril (1 mg/kg or 3 mg/kg), or BIBR-277 (3 mg/kg) was injected i.v. 10 min before ligation. D-Arginyl-L-arginlyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl -3-(2-thi enyl)-L-alanyl-L-seryl-D-1,2,3, 4-tetrahydro-3-isoquinolinecarbonyl-L-(2alpha, 3beta, 7abeta)-octahydro-1H-indole-2-carbonyl-L-arginine (Hoe-140), a bradykinin B(2) receptor antagonist, at 300 microg/kg was injected i. v. 10 min before drug injection. Contractile function was assessed on the basis of percentage segment shortening (%SS). ATP levels were measured in 60-min reperfused hearts. %SS significantly decreased during ischemia, and recovered during reperfusion, although the %SS was significantly less than the pre-ischemic level. Both enalapril at either dose and BIBR-277 significantly enhanced %SS recovery during reperfusion, an effect which was associated with a tendency toward energy preservation. Hoe-140 completely abolished the effect of enalapril at either dose, while it did not modify that of BIBR-277. Inhibition of angiotensin II formation and bradykinin breakdown may be separately related to the improvement of myocardial stunning.
Nakai
T
T
Department of Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka, Otaru, Japan.
Satoh
K
K
Kosugi
T
T
Hoshi
K
K
Ichihara
K
K
D000255:Adenosine Triphosphate / Q000032:analysis; D000758:Anesthesia; D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008026:Ligation; D008297:Male; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000378:metabolism* / Q000503:physiopathology*; D000077333:Telmisartan; D013997:Time Factors; D017725:Ventricular Pressure / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D065168:Bradykinin Receptor Antagonists; D000804:Angiotensin II; D004656:Enalapril; C065679:icatibant; D000255:Adenosine Triphosphate; D001920:Bradykinin; D000077333:Telmisartan