瞬时受体电位通道_高血压治疗的新靶点.pptVIP

Effect of CCB/SKF on Angiotensin II-induced aortic contraction and calcium increase in VSMC from SHR Vasomotion occurs in arteries either spontaneously or in response to pressure, stretch or application of vasoconstrictor agonists, which is associated with slow oscillations of smooth muscle membrane potential and of intracellular calcium concentrations. Vasomotion may also be enhanced by oscillations of transplasmamembrane calcium influx. TRP channels have been described to play an important role for calcium influx. What is pathophysiological relevance of vasomotion ? In several experimental models of hypertension an increased vasomotion of arteries had been described. Lefer et al. observed enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats compared to normotensive rats (Lefer et al., 1990). An increased vasomotion was observed in segments of posterior cerebral arteries and in mesenteric arteries from spontaneously hypertensive stroke-prone rats compared to Wistar-Kyoto rats(Osol Halpern 1988; Tsai et al., 1995). Vasomotion of coronary artery causes cardiac ischemia. Norepinephrine (NE) caused a rapid vasonconstriction and followed by synchronized oscillations of vascular tone (vasomotion) in mesenteric artery rings from SHR Immunohistochemistry shows TRPCs distribution in mesenteric arteries Inhibition of TRPC significantly attenuates NE-induced vasomotion in SHR Specific antagonizing TRP Channel subtypes significantly reduced vasomotion Effects of ARB and CCB on vasomotion and systolic blood pressure in SHR Effects of ARB and CCB on TRPCs expression of mesenteric artery ACKNOWLEDGMENS Increased expression of TRPC1, TRPC3, TRPC5 in mesenteric artery from SHR Inhibition of NE-induced vasomotion in mesenteric arteries from SHR by specific TRPC antibodies TRPC1 Control Control TRPC3 Inhibition of NE-induced calcium increase in mesenteric arteries from SHR by specific TRPC antibodies Ctr Amlo Telm