Renal Denervation Sensitizes Renal Resistance Arteries to L‐type Ca2+ Channel Activation

Abstract

We have shown that a depolarized vascular smooth muscle cell (VSMC) membrane potential sensitizes renal resistance arteries of sympathectomized rats to L‐type Ca2+‐channel activation. We tested if local renal denervation induces a similar alteration. Further, we investigated the contribution of ATP‐dependent potassium (KATP) channels for the regulation of renal resistance artery tone and tested if a depolarized VSMC membrane potential contributes to the increase in renal arterial norepinephrine (NE) sensitivity that develops after sympathectomy and renal denervation.Renal resistance arteries were obtained from rats that underwent neonatal sympathectomy, local renal denervation or respective sham‐treatments. In addition, interlobular and distal arcuate arteries were dissected from human kidney samples. Vessels were investigated by small vessel myography. Cumulative concentration‐response curves (CRCs) were obtained for the L‐type Ca2+ channel activator S‐(−)‐BayK8644 and NE in the absence or presence of glibenclamide (KATP channel blocker) and levcromakalim (KATP channel activator).Maximum S‐(−)‐BayK8644‐induced wall tension was 70% of maximum K+‐induced wall tension in arteries from sympathectomized and renal denervated rats vs. 30% of maximum K+‐induced wall tension in controls (p < 0.05). In human intrarenal arteries maximum S‐(−)‐BayK8644‐induced tension was 100% of K+‐induced tension. Levcromakalim (1 μM) abolished S‐(−)‐BayK8644 induced vasoconstrictions in rat and human arteries. Compared to respective controls, arteries from sympathectomized and renal denervated rats showed a leftward shift of the NE CRCs. Glibenclamide did not affect basal and NE‐induced wall tension in rat and human renal resistance arteries. Levcromakalim induced similar rightward shifts of the NE CRCs in vessels from sympathectomized, renal denervated and sham‐treated rats (DlogEC50 −0.58 – −0.27 M) and significantly blunted NE‐induced vasoconstrictions in human renal resistance arteries.L‐type Ca2+ channel activation is facilitated in renal resistance arteries of locally denervated kidneys suggesting that VSMC membrane potential is depolarized compared to VSMC from innervated kidneys. KATP channels are functional in rat and human renal resistance arteries. They play a minor role for the maintenance of basal tone but may mediate agonist‐induced vasodilation. The data further suggest that VSMC membrane potential depolarization does not significantly contribute to sympathectomy‐ and denervation‐induced NE supersensitivity in renal resistance arteries.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.