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

作者：Bencze Michal^*; Behuliak Michal; Vavrinova Anna; Zicha Josef

来源：Life Sciences, 2016, 166: 46-53.

DOI：10.1016/j.lfs.2016.10.005

• Femoral artery
• SHR
• Vascular contractility
• Adrenergic contraction
• Tyramine
• Propranolol
• Neuropeptide Y

Aims: 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 alpha-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 beta-adrenoceptors by propranolol or selective beta(2)-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 alpha- and beta-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.

• 出版日期2016-12-1