Activation of KCa3.1 by SKA-31 induces arteriolar dilatation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice.

摘要: Background and Purpose The calcium-activated potassium channel KCa3.1 is expressed in the vascular endothelium where its activation causes endothelial hyperpolarization initiates endothelium-derived (EDH)-dependent dilatation. Here, we investigated whether pharmacological of dilates skeletal muscle arterioles myoendothelial gap junctions formed by connexin40 (Cx40) are required for EDH-type dilatations pressure depressor responses vivo. Experimental Approach We performed intravital microscopy cremaster microcirculation blood telemetry Cx40-deficient mice. Key Results In wild-type mice, KCa3.1-activator SKA-31 induced pronounced concentration-dependent arteriolar dilatations, amounting to ∼40% maximal dilatation, enhanced effects ACh. These were absent mice devoid channels. In contrast, SKA-31-induced not attenuated with cells deficient Cx40 (Cx40fl/fl:Tie2-Cre). isolated cell clusters, hyperpolarizations similar magnitudes (by ∼38 mV) Cx40fl/fl:Tie2-Cre, ubiquitous (Cx40-/-) controls (Cx40fl/fl), which reversed specific KCa3.1-blocker TRAM-34. normotensive Cx40fl/fl:Tie2-Cre as well hypertensive Cx40-/- animals, i.p. injections (30 100 mg·kg−1) decreased arterial ∼32 mmHg all genotypes. The response 100 mg·kg−1 was associated a decrease heart rate. Conclusions Implications We conclude that evoked channels induces independent Cx40-containing junctions. As reduced activators may be useful drugs severe treatment-resistant hypertension.