Castellano M, Rizzoni D, Beschi M, Böhm M, Porteri E, Bettoni G, Cinelli A, Rosei E A
Department of Scienze Mediche, University of Brescia, Italy.
J Cardiovasc Pharmacol. 1995 Sep;26(3):381-7. doi: 10.1097/00005344-199509000-00006.
We investigated the effects of chronic treatment with the angiotensin-converting enzyme (ACE) inhibitor fosinopril on cardiac and vascular noradrenergic neurotransmission as related to cardiovascular hypertrophy in spontaneously hypertensive rats (SHRs). SHRs were treated with fosinopril at "high dose" (SHR-HD, 25 mg/kg/day) or "low dose" (SHR-LD, 1 mg/kg/day) from the 6th to the 12th week of age, and compared to age-matched untreated SHRs (SHR-C) and Wistar-Kyoto controls (WKY). Blood pressure was significantly reduced in SHR-HD but not in SHR-LD when compared to SHR-C. The antihypertensive dose of fosinopril reduced both cardiac and vascular hypertrophy, whereas the low dose was effective only in reducing vascular hypertrophy. Several differences in presynaptic and postsynaptic cardiovascular noradrenergic neurotransmission were observed between SHR-C and WKY rats (increased cardiac norepinephrine concentration, down-regulation of cardiac beta-adrenoceptors, reduced alpha-adrenergic receptor-mediated vasoconstrictor response of small mesenteric arteries to exogenous norepinephrine). All these differences were abolished by ACE inhibitor treatment, both at antihypertensive or at subantihypertensive doses. The results of this study are consistent with the hypothesis that chronic ACE inhibition may exert an inhibitory modulation on the peripheral adrenergic transmission, which is not related to blood pressure reduction. This modulation does not appear to be a determinant in preventing the development of cardiac hypertrophy but may play a role in the regression of vascular structural alterations in spontaneously hypertensive rats.
我们研究了血管紧张素转换酶（ACE）抑制剂福辛普利长期治疗对自发性高血压大鼠（SHR）心脏和血管去甲肾上腺素能神经传递的影响，以及与心血管肥大的关系。从6周龄至12周龄，对SHR分别给予“高剂量”（SHR-HD，25mg/kg/天）或“低剂量”（SHR-LD，1mg/kg/天）的福辛普利治疗，并与年龄匹配的未治疗SHR（SHR-C）和Wistar-Kyoto对照大鼠（WKY）进行比较。与SHR-C相比，SHR-HD组血压显著降低，而SHR-LD组血压无明显变化。福辛普利的降压剂量可减轻心脏和血管肥大，而低剂量仅能有效减轻血管肥大。在SHR-C和WKY大鼠之间观察到突触前和突触后心血管去甲肾上腺素能神经传递存在一些差异（心脏去甲肾上腺素浓度增加、心脏β-肾上腺素能受体下调、小肠系膜动脉对外源性去甲肾上腺素的α-肾上腺素能受体介导的血管收缩反应降低）。ACE抑制剂治疗，无论是降压剂量还是亚降压剂量，均消除了所有这些差异。本研究结果与以下假设一致：长期ACE抑制可能对外周肾上腺素能传递产生抑制性调节作用，这与血压降低无关。这种调节似乎不是预防心脏肥大发展的决定因素，但可能在自发性高血压大鼠血管结构改变的消退中起作用。
