Improvement in baroreflex function by an oral angiotensin receptor antagonist in rats with myocardial infarction.
Impaired baroreflex function is a factor responsible for poor prognosis in myocardial infarction patients. Using logistic function curves, we calculated the maximal gain of the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate in conscious Wistar-Kyoto and spontaneously hypertensive rats whose left anterior descending artery had been ligated 4 weeks earlier. We further investigated whether 3-week oral treatment with the angiotensin II type 1 receptor antagonist TCV-116 would improve the baroreflex in rats with myocardial infarction. The maximal gain of the mean arterial pressure-RSNA relation in spontaneously hypertensive rats with myocardial infarction and treated with vehicle (1.7 +/- 0.1% control per mm Hg) was smaller than the gain in sham-operated hypertensive rats (2.3 +/- 0.1% control per mm Hg). After 3-week oral treatment with TCV-116, the maximal gain of the arterial pressure-RSNA relation in hypertensive rats with myocardial infarction was 2.3 +/- 0.1% control per mm Hg and significantly greater than the gain in infarcted and vehicle-treated hypertensive rats. In hypertensive rats, the maximal gain of the arterial pressure-heart rate relation of infarcted and TCV-116-treated rats was larger than in infarcted and vehicle-treated rats but significantly smaller than in sham-operated rats. These results demonstrate that oral treatment with an angiotensin receptor antagonist is effective in restoring the impaired baroreflex caused by myocardial infarction and that endogenous angiotensin II is one of the critical factors involved in the impaired baroreflex in myocardial infarction.
Nishizawa
M
M
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Kumagai
H
H
Ichikawa
M
M
Oshima
N
N
Suzuki
H
H
Saruta
T
T
D000284:Administration, Oral; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011355:Prodrugs; D013777:Tetrazoles; C077793:candesartan cilexetil