title: Ginkgo biloba extract (EGb 761) normalizes hypertension in 2K, 1C hypertensive rats: role of antioxidant mechanisms, ACE inhibiting activity and improvement of endothelial dysfunction.
abstract: 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, 180 mg/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 (MDA) 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. Endothelium-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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Suzan M
authors.initials: SM
authors.lastname: Mansour
authors.forename: Ashraf K
authors.initials: AK
authors.lastname: Bahgat
authors.forename: Aiman S
authors.initials: AS
authors.lastname: El-Khatib
authors.forename: Mohamed T
authors.initials: MT
authors.lastname: Khayyal
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020441:Ginkgo biloba / Q000737:chemistry; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D000096983:Ginkgo Extract
chemical_list: D000109:Acetylcholine; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000975:Antioxidants; D007703:Peptidyl-Dipeptidase A; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract