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The Functional Contribution Of Myoendothelial Feedback To Arterial Tone Is Determined By The Nature Of The Vasoconstricion
Abstract   Peer reviewed

The Functional Contribution Of Myoendothelial Feedback To Arterial Tone Is Determined By The Nature Of The Vasoconstricion

Paul M Kerr, Ran Wei, Stephanie E Lunn, Stephen L Gust, Boyd Classen, Timothy V Murphy, Shaun L Sandow and Frances Plane
FASEB Journal, Vol.31(Supplement 1)
Annual Meeting of the American-Society-for-Pharmacology-and-Experimental-Therapeutics (ASPET) at Experimental Biology Meeting (Chicago, United States, 22-Apr-2017–26-Apr-2017)
2017
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Abstract

Biochemistry and Cell Biology Physiology Medical Physiology
Constriction of resistance arteries in response to global application of agonists is modulated by activation of the endothelium via myoendothelial feedback. Recent evidence supports a model of myoendothelial feedback in which generation of localized InsP3-dependent Ca2+ transients leads to activation of intermediate conductance Ca2+-activated K+ (IKCa) channels to hyperpolarize the endothelium. We have now investigated the functional contribution of this pathway to limiting responses to two physiologically important vasoconstrictor stimuli, activation of sympathetic nerves and increases in intravascular pressure. In isolated segments of rat mesenteric resistance artery mounted in a wire or pressure myograph, pharmacological inhibition of IKCa channels significantly potentiated increases in tone elicited by global application agonists such as noradrenaline, but did not significantly alter increases in tone elicited by stimulation of sympathetic perivascular nerves, or myogenic reactivity elicited by step-wise increases in intravascular pressure. Similarly, in the endothelium-intact perfused mesenteric bed, blockers of IKCa channels enhanced vasoconstriction to exogenous noradrenaline but had no effect on nerve-evoked vasoconstriction. However, the influence of the endothelium on responses to sympathetic nerve stimulation was inhibited by blockers of nitric oxide signaling and by inhibition of small conductance Ca2+-activated K+ (SKCa) channels. These data demonstrate that the contribution of myoendothelial feedback to endothelium-dependent modulation of tone is determined by the stimulus for smooth muscle contraction. Although activated by global application of contractile agonists, the myoendothelial feedback pathway does not appear to play a significant role in modulating myogenic reactivity or nerve-evoked responses in resistance arteries. Furthermore, in the intact mesenteric vascular bed, under conditions of constant flow, increases in shear stress rather than myoendothelial feedback, may be the predominant stimulus for engagement of the endothelium to oppose nerve-evoked vasoconstriction.

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