| BACKGROUND Studies have shown that exaggerated vascular production of reactive oxygen species(ROS) promotes the development of endothelial dysfunction in hypertension. However,the mechanism is not well understood. Recent studies suggest the predominant source of ROS production in the vessel wall is nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate(NADH/NADPH) oxidase system. P22phox is a critical component of NAD(P)H oxidase and plays an important role in gernerating ROS. New studies show that angiotensin type 1(AT1) receptor inhibitors decrease NAD(P)H oxidase activity. This suggests AT1 receptor may be associated with increase of ROS in vessel wall,because activation of the renin-angiotensin system(RAS) is the key mechanism in development of hypertension. Relationship between AT1 receptor and ROS has not been previously investigated in Chinese. Statins improve endothelial function of hypercholesterolemia. However,it is not clear whether statins improve endothelial dysfunction of normocholesterolemic spontaneously hypertensive rats(SHR) and patients with essential hypertension(EH).OBJECTIVE To investigate the changes and association of ROS,AT1 receptor and p22phox mRNA expression in aorta of SHR,the relationship between ROS and endothelium- dependent vasodilation of normocholesterolemic patients with EH and the effects of atorvastain.METHODS 1. 18-week-old SHR were randomly assigned to two groups: SHR group (vehicle once daily , n=7), T-SHR group(atorvastain,50mg/kg/day,n=8). WKY group(vehicle once daily ,n=10) were used as control. After treatment of 30 days,blood samples were taken for the determination of concentrations of plasma Ang II,serum superoxide dismutase(SOD) and nitric oxide(NO). Vascular production of ROS was assessed by lucigenin chemiluminescence assays. AT1 receptor protein in aorta was measured using immunohistochemistric assays. AT1 receptor and p22phox mRNA in aorta were quantified with semiquantitative RT-PCR methodology.2. 60 patients with EH were randomly divided into two groups:control group (n=30) and experimental group (n=30). They were all treated with hydrochlorothiazide (12.5~25mg qd) and betaloc (12.5~25mg bid~tid) for two months. Atorvastain(10mg qn) was added in experimental group. Concentrations of plasma Ang II,serum SOD,NO,lipids,ALT and endothelium-dependent vasodilation were measured in the beginning and end of therapy.RESULTS l.In SHR group, concentration of plasma Ang II ,production of vascular ROS,accumulation of AT] receptor in aorta and mRNA expression of AT] receptor and p22phox significantly increased,while levels of serum SOD and NO significantly decreased as compared to those in WKY(P<0.01). These changes in SHR were significantly ameliorated by administration of atorvastain.In T-SHR group, concentration of plasma Ang II,production of vascular ROS,accumulation of AT1 receptor in aorta and mRNA expression of AT1 receptor and p22phox significantly decreased,and levels of serum SOD,NO significantly increased as compared to those in SHR(P<0.01). Vascular ROS was positively correlated with blood pressure, AT1 receptor and p22phox mRNA expression,and the coefficients were 0.9(P<0.01),0.951(P<0.01),0.944(P<0.01). It was negatively correlated with serum SOD and NO,and the coefficients were -0.951 (P<0.01),-0.893(P<0.01).2. Concentration of plasma Ang II in patients with EH was significantly elevated and levels of serum SOD,NO were reduced in hypertensive subjects compared to normotensive subjects(P<0.01).The increased percentage of the brachial artery diameter after reactive hyperemia was lower in patients with EH than that in normal controls(6.82 2.69%vsl2.01 3.07%,P<0.001),whereas nitroglycerin induced changes were similar(p>0.05). Endothelium-dependent vasodilation was negatively correlated with plasma Ang II,and the coefficient was -0.87 (P<0.01). It was positively correlated with serum SOD,NO,and the coefficients were 0.547 (P<0.01),0.791(P<0.01).3.Treatment with hydrochlorothiazide and betaloc for two months normali...
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