title: Increased rhythmicity in hypertensive arterial smooth muscle is linked to transient receptor potential canonical channels.
abstract: Vasomotion describes oscillations of arterial vascular tone due to synchronized changes of intracellular calcium concentrations. Since increased calcium influx into vascular smooth muscle cells from spontaneously hypertensive rats (SHR) has been associated with variances of transient receptor potential canonical (TRPC) channels, in the present study we tested the hypothesis that increased vasomotion in hypertension is directly linked to increased TRPC expression. Using a small vessel myograph we observed significantly increased norepinephrine-induced vasomotion in mesenteric arterioles from SHR compared to normotensive Wistar-Kyoto (WKY) rats. Using immunoblottings we obtained significantly increased expression of TRPC1, TRPC3 and TRPC5 in mesenteric arterioles from SHR compared to WKY, whereas TRPC4 and TRPC6 showed no differences. Norepinephrine-induced vasomotion from SHR was significantly reduced in the presence of verapamil, SKF96365, 2-aminoethoxydiphenylborane (2-APB) or gadolinium. Pre-incubation of mesenteric arterioles with anti-TRPC1 and anti-TRPC3 antibodies significantly reduced norepinephrine-induced vasomotion and calcium influx. Control experiments with pre-incubation of TRPC antibodies plus their respective antigenic peptide or in the presence of anti-β-actin antibodies or random immunoglobulins not related to TRPC channels showed no inhibitory effects of norepinephrine-induced vasomotion and calcium influx. Administration of candesartan or telmisartan, but not amlodipine to SHR for 16 weeks significantly reduced either the expression of TRPC1, TRPC3 and TRPC5 as well as norepinephrine-induced vasomotion in mesenteric arterioles. In conclusion we gave experimental evidence that the increased TRPC1, TRPC3 and TRPC5 expression in mesenteric arterioles from SHR causes increased vasomotion in hypertension.
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Luo
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Feng
authors.forename: Tingbing
authors.initials: T
authors.lastname: Cao
authors.forename: Liqun
authors.initials: L
authors.lastname: Ma
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000503:physiopathology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D015220:Calcium Channels / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology*; D010507:Periodicity; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D050052:TRPC Cation Channels / Q000378:metabolism*; D000077333:Telmisartan; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D001896:Boron Compounds; D015220:Calcium Channels; D007093:Imidazoles; D050052:TRPC Cation Channels; D013777:Tetrazoles; D017311:Amlodipine; D014700:Verapamil; C109986:2-aminoethoxydiphenyl borate; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; C081643:candesartan; D002118:Calcium; D000077333:Telmisartan; D009638:Norepinephrine