Takeda K, Fujita H, Nakamura K, Uchida A, Tanaka M, Itoh H, Nakata T, Sasaki S, Nakagawa M
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Blood Press Suppl. 1994;5:94-8.
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.
为了确定血管紧张素II受体拮抗剂（AT拮抗剂）是否能改善受损的冠脉循环，并诱导高血压心脏的心肌肥厚消退，以及阐明冠状动脉中的一氧化氮系统是否参与了这一机制，将AT1拮抗剂TCV-116（10毫克/千克）口服给予自发性高血压大鼠（SHR）和Wistar Kyoto大鼠（WKY），并在离体心脏中测量冠脉血流量。用TCV进行为期2周的治疗后，SHR的高收缩压显著降低。TCV治疗后，SHR的左心室（LV）肥厚消退，而WKY的LV重量未降低。在Langendorff装置中通过输注腺苷（10^(-5) M）获得的总最小冠脉血管阻力（MCVR）在SHR中显著高于WKY。TCV治疗后，SHR中升高的MCVR降低。用NG-单甲基-L-精氨酸单乙酸盐（L-NMMA）进行冠脉灌注可增加WKY的冠脉血管阻力（CVR），而在SHR中未能增加CVR。TCV治疗恢复了SHR对L-NMMA的反应。这些发现表明，AT1拮抗剂TCV-116降低了SHR的高血压，同时改善了受损的冠脉循环，并诱导了心肌肥厚的消退。SHR冠脉血管中被抑制的一氧化氮（NO）系统似乎通过TCV治疗而被激活。
