NAD(P)H Oxidase-derived ROS Mediate Vasoconstriction Induced By Ang Ⅱ In Renal Hypertensive Rats

Hypertension is one of the most common cardiovascular diseases. The incidence of the disease was as high as 18.8%and increased very quickly.However,the mechanism of hypertension is not completely known.The enhanced tension of vascular is a hallmark of hypertension and the degree of vascular remodeling(VR)is prognostic for survival in the hypertensive state.The tension of vascular,which is enhanced in the hypertensive state,contributes to an increase in VR in the hypertensive state.Previous studies suggested the abnormal action of Angâ…¡and AT₁ receptor in vascular smooth muscle(VSM)played an important part in vasoconstriction in hypertension.However,the mechanism responsible for the enhancement of the tension induced by Angâ…¡in VSM is not well understood.In the present study,we investigated the role of ROS in the regulatory effect of Angâ…¡on vasoconstriction and further elucidated the vascular mechanism responsible for modulation of the blood pressure.It will lay a foundation in finding new drugs for management of hypertension.The study was carried out on isolated rings of femoral artery with endothelium removal in renal hypertensive rats(RHR)and those age-matched controls(Sham).Tension of VSM was recorded.Vascular reactivity to vasoactive substances was evaluated by the change of tension in rings of femoral artery.Superoxide anion level was measured with lucigenin-enhanced chemiluminescent method.Malondialdehyde (MDA)was determined by the thiobarbituric acid(TBA)spectrometric method,which indirectly indicated the ROS level in VSM.The primary findings were as follows.1.Study on the role of ROS in modulating of the tension of VSM and mediating the effect of Angâ…¡on vasoconstriction.Superoxide scavenger tempol or tiron showed a weak inhibitory effect on the enhanced tension in RHR and had no significant effect of the tension in Sham.Pretreatment with tempol or tiron significantly blocked the enhanced tension of VSM induced by Angâ…¡in both RHR and Sham. Superoxide dismutase(SOD)inhibitor diethyldithio-carbamic acid (DETC)augmented the tension of VSM in RHR,but did not significantly potentiate the effect of Angâ…¡on vasoconstriction in both RHR and Sham.Incubation of Angâ…¡,which elicited vasoconstriction,significantly increased MDA and superoxide anion levels in HR,and these effects were abolished by pretreatment with AT₁ receptor antagonist losartan in both RHR and Sham. 2.Study on the major source of the ROS in modulating the enhanced tension of VSM and mediating the vasoconstriction of Angâ…¡in RHR.NAD(P)H oxidase inhibitor apocynin showed a weak inhibitory effect on the enhanced tension in RHR and had no significant effect of the tension in Sham.Pretreatment with apocynin significantly blocked the enhanced tension induced by Angâ…¡in both RHR and Sham.In conclusion,the ROS in VSM are involved in the modulation of the enhanced tension of the VSM and contributed to the excitory effect of Angâ…¡on the vasoconstriction in RHR,the NAD(P)H oxidase is the major source of the ROS.