Unequal effects of renin-angiotensin system inhibitors in acute cardiac dysfunction induced by isoproterenol.
Several clinical trials have demonstrated that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) are equally effective in the treatment of chronic heart failure. However, this has not been confirmed for acute cardiac dysfunction. We examined whether ACEI or ARB prevents isoproterenol-induced acute left ventricular (LV) dysfunction in dogs. LV dysfunction induced by a large dose of isoproterenol (1 microg.kg(-1).min(-1), 3-h infusion) was compared in dogs treated with ACEI (temocaprilat) or ARB (olmesartan). Atrial pacing induced a constant heart rate and use of adjustable aortic banding provided a nearly constant afterload. LV systolic function (LV dP/dt, fractional shortening, and ejection fraction) and diastolic function (tau and LV end-diastolic pressure) were significantly deteriorated after isoproterenol infusion. The LV dysfunction was almost totally prevented by ARB but was only partially prevented by ACEI. The partial effect of ACEI was complemented by cotreatment with HOE-140, a bradykinin B2 receptor antagonist. At baseline, the response to low doses of isoproterenol was significantly attenuated by ACEI but not by ARB, and the ACEI-induced attenuation was totally abolished by cotreatment with HOE-140. The response to isoproterenol was significantly attenuated after 3 h of excess isoproterenol loading, and it was almost completely preserved by ARB but not by ACEI. In conclusion, acute LV dysfunction and beta-adrenergic desensitization induced by excess isoproterenol administration were almost totally prevented by ARB but only partially prevented by ACEI. These differences were attributable at least in part to bradykinin pathways activated by ACEI administration in acute LV dysfunction.
First Dept. of Internal Medicine, Asahikawa Medical College, 2-1-1 Midorigaoka higashi, Asahikawa, Hokkaido 078-8510, Japan.
Takafumi
T
Ohta
Naoyuki
N
Hasebe
Shiro
S
Tsuji
Kazuma
K
Izawa
Yin-Tie
YT
Jin
Shinsuke
S
Kido
Syunsuke
S
Natori
Motohiko
M
Sato
Kenjiro
K
Kikuchi
D000208:Acute Disease; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology*; D016277:Ventricular Function, Left
D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin; D007545:Isoproterenol