Altered contractile responses of arteries from spontaneously hypertensive rat: The role of endogenous mediators and membrane depolarization

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• 作者：Michal Bencze^a ; ^{michalbencze@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Michal Behuliak^a ; Anna Vavří ; nová ; ^a ; ^b ; Josef Zicha^a
• 关键词：αAB ; α-adrenoceptor blockade ; BIBP ; BIBP-3226 ; BKCa ; large conductance calcium-activated potassium channel ; FLUP ; flupirtine ; L-VDCC ; L-type voltage-dependent calcium channel ; ICI ; ICI-118 ; 551 ; KV ; voltage-dependent potassium channels ; KPSS ; K+-substituted physiological saline solution ; NE ; norepinephrine ; NIF ; nifedipine ; NPY ; neuropeptide Y ; PSS ; physiological saline solution ; SHR ; spontaneously hypertensive rats ; WKY ; Wistar-Kyoto rats
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：166
• 期：Complete
• 页码：46-53
• 全文大小：880 K

文摘

The goal of our study was to reveal the important mechanism(s) responsible for the enhanced contractility of isolated arteries from animals suffering genetic hypertension.

Main methods

Contractile force of endothelium-denuded arteries, modulated by various interventions, was measured by wire myography.

Key findings

Spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) arteries were stimulated by norepinephrine, increased extracellular K⁺ or tyramine. Strain difference was not observed in the contraction elicited by exogenous norepinephrine but SHR arteries responded more to tyramine (causing endogenous norepinephrine release from neuronal varicosities). K⁺-induced contraction was enhanced in SHR arteries, with no involvement of endogenous catecholamines. The α-adrenoceptor blockade lowered tyramine-induced contraction more in SHR arteries; similar effect was achieved by guanethidine-induced sympathectomy. Partial depolarization of WKY arteries by 20 mM K⁺ enhanced its contraction to SHR level. The blockade of β-adrenoceptors by propranolol or selective β₂-antagonist ICI-118,551 induced contraction of SHR endothelium-denuded arteries but was without significant effects on WKY arteries unless they were stimulated with K⁺. Both tyramine-induced and propranolol-induced contractions were attenuated by flupirtine and abolished by nifedipine.

Significance

The differences of SHR and WKY arteries were not related to vascular expression of α- and β-adrenoceptors or G-proteins. Enhanced contractility of SHR arteries is related to both increased presence of endogenous norepinephrine in vascular wall and also to altered vascular smooth muscle membrane potential.