Effect of an angiotensin II receptor antagonist, TCV-116, on cardiac hypertrophy and coronary circulation in spontaneously hypertensive rats.
To determine whether an angiotensin II receptor antagonist (AT antagonist) could improve the impaired coronary circulation as well as induce regression of cardiac hypertrophy in the hypertensive heart, and to elucidate whether the nitric oxide system in the coronary artery was involved in this mechanism, the AT1 antagonist, TCV-116 (10 mg/kg), was administered orally to spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY), and coronary flow was measured in the isolated hearts. High systolic blood pressure in SHR was significantly reduced by a 2-week treatment with TCV. Left ventricular (LV) hypertrophy in SHR regressed after TCV treatment, while LV weight in WKY was not reduced. Total minimum coronary vascular resistance (MCVR) obtained with adenosine (10(-5) M) infusions in a Langendorff apparatus was significantly greater in SHR than in WKY. Increased MCVR in SHR was reduced after TCV treatment. Coronary perfusion with NG-monomethyl-L-arginine monoacetate (L-NMMA) increased coronary vascular resistance (CVR) in WKY, while it failed to increase CVR in SHR. TCV treatment restored the responses to L-NMMA in SHR. These findings suggest that the AT1 antagonist, TCV-116, lowered the high blood pressure in SHR, concomitantly improving the impaired coronary circulation, and that it induced regression of the cardiac hypertrophy. The suppressed nitric oxide (NO) system in the coronary vessels in SHR appeared to be activated by TCV treatment.
Takeda
K
K
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Fujita
H
H
Nakamura
K
K
Uchida
A
A
Tanaka
M
M
Itoh
H
H
Nakata
T
T
Sasaki
S
S
Nakagawa
M
M
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles; D014655:Vascular Resistance / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011355:Prodrugs; D013777:Tetrazoles; D009569:Nitric Oxide; D001120:Arginine; C077793:candesartan cilexetil; D019331:NG-Nitroarginine Methyl Ester