The Compensatory Effect And Pathophysiologic Meaning Of TRPC In Aortic Vascular Smooth Muscle In Hypertension

Aims:The compensatory effect and pathophysiologic meaning of TRPC in aortic vascular smooth muscle in hypertension.Methods:We selected renal artery narrowing and Spontaneously Hypertensive Rat (SHR) as animal models. We observed the change of TRPC family in aortic vascular smooth muscle and mesenteric arterial smooth muscle in the remodeling process using electrophysiological Pharmacology and molecular biology techniques.Results:(1) In normal and hypertensive vascular smooth muscle in vitro animal experiments, agonists of TRPC channel, Ang II significantly increased thoracic aortic smooth muscle tension. Non-specific blockers of TRPC channel nickel chloride or SKF significantly block the effect of Ang Ⅱ; (2) The contractile response of renal artery narrowing and SHR rat thoracic aortic smooth muscle to Ang Ⅱ, the TRPC channel agonist, were significantly reduced; (3) In the absence of extracellular calcium, the effect of Ang Ⅱ increased the tension of vascular smooth.muscle of hypertensive rats was much more than that of normal animals. Otherwise the reaction to Ang Ⅱ in the case of extracellular calcium of hypertensive rats significantly decreased; (4) In the absence of extracellular calcium and the presence of Ang Ⅱ, the non-specific blocker of TRPC nickel chloride or SKF pretreatment, can almost completely block reload calcium which leads to increased tension effect; (5) Western Blotting show that, The expression of TRPC1, TRPC3, TRPC4, TRPC6 in Model group hypertensive rat aortic smooth muscle arch, thoracic aorta smooth muscle, abdominal aorta and superior mesenteric artery smooth muscle was significantly down-regulated; Thoracic aorta of spontaneously hypertensive rat ooth muscle TRPC1, TRPC3 expression was significantly down-regulated; (6) Significant in the thoracic aorta smooth muscle, abdominal aorta and superior mesenteric artery smooth muscle Aortic smooth muscle of model group and the spontaneously hypertensive rats, the expression of Ang Ⅱ receptor ATI was significantly increased.Conclusions:The results suggest that in the pathogenesis of hypertension, Vasoactive Ang Ⅱ signaling pathway activity was significantly upregulated, but hypertensive rat thoracic aortic smooth muscle response to Ang Ⅱ was significantly lower than the control group; This reaction may be related to downregulation of vascular smooth muscle TRPC. In the early onset of hypertension, vascular smooth muscle TRPC down, vasoconstrictor response to high blood pressure may cause increased sensitivity to the role of a compensatory, excessive rise in blood pressure and can buffer revascularization and other pathological reactions. Our results may have theoretical significance for elucidating the pathogenesis of hypertension and potential clinical value.