Yamazaki T, Uematsu T, Mizuno A, Takiguchi Y, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Arch Int Pharmacodyn Ther. 1989 May-Jun;299:155-68.
Aortic insufficiency (AI) was produced in rats by puncturing one of the aortic valves with a plastic rod inserted from the right carotid artery, and the subsequent changes in alpha- and beta-adrenoceptors and Ca2+ channels were investigated by means of radioligand binding assays. The positive inotropic effects of methoxamine (Met), isoproterenol (Iso) and Ca2+ were also examined in isolated left papillary muscles. The ratio of the whole heart weight to body weight in AI rats increased significantly as compared with sham-operated rats from 1 till 8 weeks after operation, showing that a cardiac hypertrophy had occurred due to the volume overload. Maximum binding sites (Bmax) for 3H-prazosin in cardiac ventricular muscles of AI rats significantly increased at 4 weeks and returned to the control level at 8 weeks when the AI was still patent. Bmax for 3H-dihydroalprenolol (3H-DHA) of AI rats significantly increased at 2 and 4 weeks and returned to the control level at 8 weeks. Bmax for 3H-nitrendipine binding of AI rats significantly decreased at 2 weeks and returned to the control level at 4 weeks. Affinities for these bindings, as expressed by values of dissociation constants, showed no significant changes. The sensitivities of papillary muscles to Met and Iso were significantly increased in AI rats at 4 weeks. Plasma immunoreactive alpha-atrial natriuretic polypeptide (alpha-ANP) concentration of AI rats tended to increase from 1 till 3 weeks and returned to the control level at 4 weeks but these changes were not significant. We conclude that the synthesis of new adrenoceptors keeps pace with the hypertrophic process and may even overshoot during a short period.
通过从右颈动脉插入一根塑料棒穿刺大鼠的一个主动脉瓣来制造主动脉瓣关闭不全（AI），并通过放射性配体结合试验研究随后α-和β-肾上腺素能受体以及Ca2+通道的变化。还在离体左乳头肌中检测了甲氧明（Met）、异丙肾上腺素（Iso）和Ca2+的正性肌力作用。与假手术大鼠相比，AI大鼠的全心重量与体重之比在术后1至8周显著增加，表明由于容量负荷过重发生了心肌肥大。AI大鼠心室肌中3H-哌唑嗪的最大结合位点（Bmax）在4周时显著增加，在8周时仍存在AI时恢复到对照水平。AI大鼠的3H-二氢阿普洛尔（3H-DHA）的Bmax在2周和4周时显著增加，在8周时恢复到对照水平。AI大鼠的3H-尼群地平结合的Bmax在2周时显著降低，在4周时恢复到对照水平。以解离常数表示的这些结合的亲和力没有显著变化。在4周时，AI大鼠乳头肌对Met和Iso的敏感性显著增加。AI大鼠的血浆免疫反应性α-心房利钠多肽（α-ANP）浓度在1至3周时趋于增加，在4周时恢复到对照水平，但这些变化不显著。我们得出结论，新的肾上腺素能受体的合成与肥大过程同步，甚至在短时间内可能会过度。
