Hypotensive and diuretic effects of camboginol and morelloflavone from garcinia dulcis in 2-kidneys-1-clip renovascular hypertensive rat

Abstract

This study aimed to evaluate hypotensive and diuretic effects of camboginol (isoprenylated benzophenone) and morelloflavone (biflavonoid), a robust antioxidant which isolated from Garcinia dulcis, in 2-kidneys-1-clip (2K1C) renovascular hypertensive rats together with their vasorelaxant mechanisms. Male Wistar rats (150-200 g) were undergone either 2K1C or sham operation (SO) (n=6, each). Four weeks later, an in vivo study was performed by which clearance markers (0.5% para- aminohippuric acid and 1% inulin) were given via a jugular vein to estimate effective renal plasma flow (ERPF) and glomerular filtration rate in anesthetized rats. Camboginol or morelloflavone was given at the dose of 0.1 mg/kg + 5 μg/min/kg body weight, while arterial blood pressure (ABP) and heart rate were monitored via a carotid artery. Plasma and urine samples were collected for determination of osmolar and free water clearances. Baroreflex sensitivity (BRS), plasma malondialdehyde (MDA) level and an expression of endothelial nitric oxide synthase (eNOS) were also investigated. For an in vitro study, the relaxation of isolated aortic ring which phenylephrine-preconstriction was experimented using an organ bath technique by cumulative additions of either camboginol or morelloflavaone (1013-105 M) in the presence or absence of specific vasorelaxant inhibitors. It was found that camboginol and morelloflavone significantly decreased ABP, increased ERPF and increased urine flow rate in anesthetized 2K1C rats. Both also improved an impaired BRS, decreased plasma MDA levels and enhanced eNOS expression in vascular endothelium. The mechanisms of their vasorelaxant action mainly involved the different extent of endothelial dependent vasorelaxation pathway. The responsive mechanisms of diuretic and hypotensive effects of camboginol and morelloflavone are likely to associate with their scavenging activity.