Angiotensin converting enzyme
The 2 kidney, 1 -clip (2K, 1C) model of hypertension was used to investigate the potential antihypertensive effect of a standardized leaf extract of Ginkgo biloba (EGb 761). Clipping of the renal artery resulted in gradual elevation of the systolic blood pressure (SBP) reaching a plateau after 4 weeks of surgery. Treatment of hypertensive rats with EGb 761 (60, 90, 180mg/kg/day orally) was therefore started 4 weeks after surgery and continued for 3 weeks. This led to a dose-dependent reduction in SBP with no significant change in heart rate. Control hypertensive rats showed a significant elevation of total protein thiols (Pr-SHs level) in both clipped and non-clipped kidneys as well as in the serum. However, glutathione peroxidase (GSH-Px) activity was decreased in the clipped kidneys but elevated in the non-clipped ones and in the blood. The malondialdehyde (IV1DA) level was raised in clipped kidneys but not in non-clipped ones nor in the serum. Nitric oxide (NO level) and angiotensin converting enzyme (ACE) activity were increased in both clipped and non-clipped kidneys but not in the serum. Enclothelium-dependent and -independent relaxation of aortic rings towards acetylcholine (Ach) and sodium nitroprusside (SNP) were impaired. Treatment with EGb 761 (180 mg/kg/day for 3 weeks) was associated with recovery of GSH-Px activity in clipped kidneys, inhibition of ACE activity in both kidneys and a reduction in the elevated NO level of the non-clipped kidneys, decreased responsiveness to the vasoconstrictor NE and improvement of endothelial function as evidenced by restoration of endothelium-dependent vasorelaxation induced by Ach. The observed beneficial effects of the EGb 761 may be attributed to different factors, including ACE inhibition and maintenance of cellular antioxidant capacity as well as preserving vascular reactivity towards endothelium-dependent and -independent vasodilators while inhibiting responses to vasoconstrictors.
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Extracts from leaves of Ginkgo biloba, a widely planted Chinese tree, have been utilized therapeutically for decades with a uniquely broad spectrum of activity (Mahadevan and Park 2008). A standardized preparation of the extract, EGb 761 (Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany) has proved to be useful in cerebral and peripheral vascular insufficiency states, where the pathophysiology involves free radicals and platelet activating factor (PAF)-related abnormalities. EGb 761 and its constituents, especially terpenoids and flavonoids, have also been reported to possess vasorelaxant properties (Duarte et al. 2001; Ibarra et al. 2003), suggesting that the extract may possess protective effects against cardiovascular disease.
In the 2K, 1C model of hypertension in rats the development and maintenance of hypertension is not merely due to the vasoconstrictor effects of angiotensin II (A-II) released through activation of the renin-angiotensin system (RAS), but also involves oxidative stress induced by AT-II (Romero and Reckelhoff 1999). AT-II has been shown to stimulate the generation of superoxide anion radical ([O.sub.2]) in cultured vascular smooth muscle cells (Griendling et al. 1994) and in intact aortae of rats made hypertensive by chronic AT-II infusion (Rajagopalan...
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