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

ABSTRACT

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 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 20mM K+ enhanced its contraction to SHR level. The blockade of ß-adrenoceptors by propranolol or selective ß2-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 ß-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.