Upregulated TRPC3 and Downregulated TRPC1 Channel Expression during Hypertension is Associated with Increased Vascular Contractility in Rat.
Upregulated TRPC3 and Downregulated TRPC1 Channel Expression during Hypertension is Associated with Increased Vascular Contractility in Rat.
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DOI：
10.3389/fphys.2011.00042
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发表时间：
2011
影响因子：
4
通讯作者：
Marrelli SP
中科院分区：
文献类型：
--
作者：
Noorani MM;Noel RC;Marrelli SP
瞬时受体电位(Trp)C1和C3(TRPC1和TRPC3)在血管平滑肌细胞中表达，被认为与血管收缩有关。在本研究中，我们观察了系统性高血压对大鼠颈动脉TRPC1/TRPC3通道表达和血管收缩功能的影响。对雄性自发性高血压大鼠(SHR)、Wistar-京都(WKY)和Long Evans(LE)大鼠的CA进行了研究。RT-PCR和Western印迹法检测TRPC1/3的表达。采用全细胞膜片钳技术评价Trp通道功能，用UTP(60 μM)刺激TRPC1/3通道。在等长张力浴中测定去内皮CA节段对UTP(1-300 μM)和苯肾上腺素(Phe；0.1 NM-10 μM)的收缩。TRPC1和TRPC3在WKY和SHR的CA中均有表达。免疫印迹显示自发性高血压大鼠的TRPC3表达水平是WKY CA的3.1 ± 的1.2倍，TRPC1的表达水平为0.5 ± 的0.2倍。分离的CA在SHR和WKY表现出对UTP的增强收缩。在UTP介导的收缩中，电压依赖性钙通道(VDCC)的激活仅发生在SHR CA。在WKY和SHR CA之间，对Phe的收缩没有改变，并且两组都参与了同样显著的VDCC激活。膜片钳显示，自发性高血压大鼠的UTP刺激电流(IUTP)明显大于正常血压的WKY和LE大鼠，其峰值(−110 mV)分别为−63 ± 24 pA和−25 ± 4 pA。我们证明，在高血压期间，UTP介导的收缩而不是Phe介导的收缩在CA中被增强。SHR CA中TRPC1的表达减少，而TRPC3的表达增加。有趣的是，VDCC的激活只对UTP介导的SHR CA的收缩起作用，而对Phe介导的收缩起到相当大的作用。我们推测，高血压时TRPC通道表达的改变导致UTP(而不是Phe)信号通路中更大的平滑肌去极化、VDCC激活和血管收缩。
Transient receptor potential (TRP) C1 and C3 (TRPC1 and TRPC3) are expressed in vascular smooth muscle cells and are thought to be involved in vascular contractility. In the present study, we determined the effect of systemic hypertension on TRPC1/TRPC3 channel expression and vascular contractility in rat carotid artery (CA). CA were studied from male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY), and Long Evans (LE) rats. TRPC1/3 expression was determined by RT-PCR and Western blot. TRP channel function was evaluated by whole-cell patch clamp, using UTP (60 μM) to stimulate TRPC1/3 channels. Contractions of endothelium-denuded CA segments to UTP (1–300 μM) and phenylephrine (Phe; 0.1 nM–10 μM) were measured in an isometric tension bath. TRPC1 and TRPC3 mRNA was present in CA of both WKY and SHR. Western blot demonstrated 3.1 ± 1.2 times greater TRPC3 expression and 0.5 ± 0.2 times TRPC1 in SHR versus WKY CA. Isolated CA showed potentiated contraction to UTP in the SHR versus WKY. Activation of voltage-dependent Ca2+ channels (VDCC) in UTP-mediated constriction only occurred in SHR CA. Contraction to Phe was unaltered between WKY and SHR CA and involved equal significant VDCC activation in both groups. Patch clamp demonstrated that the UTP-stimulated current (Iutp) was greater in SHR compared to the normotensive WKY and LE rats with peak Iutp (at −110 mV) of −63 ± 24 pA compared to −25 ± 4 pA, respectively. We demonstrate that UTP-mediated but not Phe-mediated constrictions are potentiated in the CA during hypertension. Expression of TRPC1 is decreased whereas TRPC3 is increased in SHR CA. Interestingly, VDCC activation only contributes to UTP-mediated contraction of SHR CAs whereas it contributes substantially and equally in Phe-mediated contraction. We speculate that the alteration of TRPC channel expression in hypertension leads to greater smooth muscle depolarization, VDCC activation, and vascular contractility in the UTP (but not Phe) signaling pathway.
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影响因子：
8.3
作者：
Pratt, PF;Bonnet, S;Rusch, NJ
通讯作者：
Rusch, NJ
影响因子：
8.3
作者：
Liu, Daoyan;Yang, Dachun;Tepel, Martin
通讯作者：
Tepel, Martin
影响因子：
4.5
作者：
Dietrich, Alexander;Kalwa, Hermann;Gudermann, Thomas
通讯作者：
Gudermann, Thomas
DOI：
10.1152/ajpheart.01130.2008
发表时间：
2009-07-01
影响因子：
4.8
作者：
Chen, Jie;Crossland, Randy F.;Marrelli, Sean P.
通讯作者：
Marrelli, Sean P.
影响因子：
20.1
作者：
Pesic, A;Madden, JA;Rusch, NJ
通讯作者：
Rusch, NJ