Tada Yukari, Kagota Satomi, Kubota Yoko, Nejime Namie, Nakamura Kazuki, Kunitomo Masaru, Shinozuka Kazumasa
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
Biol Pharm Bull. 2008 Jan;31(1):68-72. doi: 10.1248/bpb.31.68.
We previously demonstrated that Ginkgo biloba extract (GBE) produces an anti-hypertensive effect via enhanced vasodilation responses in young spontaneously hypertensive rats (SHR) and hepatic hypertrophy occurs with increased cytochrome P450 (CYP) mRNA expression in young rats. In the present study, to clarify whether these actions of GBE are observed in older rats, we investigated cardiovascular functions and hepatic CYP protein expressions in aged SHR fed a control diet or a diet containing 0.5% GBE for 4 weeks. In aged SHR, GBE feeding significantly increased liver weight per 100 g body weight without changing the body weight. Furthermore, significant increases in alanine aminotransferase level in serum and marked increase in CYP2B protein expression in the liver were observed in aged SHR fed GBE. On the other hand, GBE feeding did not affect blood pressure, but significantly reduced heart rate and blood flow velocity in tail arteries of aged SHR. Furthermore, GBE feeding did not affect contractile response to phenylephrine, relaxation responses to not only sodium nitroprusside but also acetylcholine, and protein levels of endothelium nitric oxide synthase and soluble guanylate cyclase in aortas of aged SHR. These results suggested that long-term GBE feeding impairs peripheral circulation due to bradycardia and hepatic function in aged SHR. Thus, in the elderly population with hypertension, the use of GBE may need to be assessed for effects on heart rate and liver function.
我们之前证明,银杏叶提取物(GBE)通过增强年轻自发性高血压大鼠(SHR)的血管舒张反应产生抗高血压作用,并且在幼鼠中随着细胞色素P450(CYP)mRNA表达增加会出现肝脏肥大。在本研究中,为了阐明GBE的这些作用是否在老年大鼠中也能观察到,我们调查了喂食对照饮食或含0.5%GBE饮食4周的老年SHR的心血管功能和肝脏CYP蛋白表达。在老年SHR中,喂食GBE显著增加了每100克体重的肝脏重量,而体重未发生变化。此外,在喂食GBE的老年SHR中,观察到血清丙氨酸转氨酶水平显著升高,肝脏中CYP2B蛋白表达明显增加。另一方面,喂食GBE不影响血压,但显著降低了老年SHR尾动脉的心率和血流速度。此外,喂食GBE不影响老年SHR主动脉对去氧肾上腺素的收缩反应、对硝普钠和乙酰胆碱的舒张反应,以及内皮型一氧化氮合酶和可溶性鸟苷酸环化酶的蛋白水平。这些结果表明,长期喂食GBE会因老年SHR的心动过缓和肝功能损害而损害外周循环。因此,在老年高血压人群中,可能需要评估使用GBE对心率和肝功能的影响。