Enhanced vasoconstriction to α1-adrenoceptor stimulation during cooling in mouse cutaneous plantar arteries

Abstract

Cutaneous arteries are known to constrict in response to cooling via α2C-adrenoceptors. The involvement of α1-adrenoceptors in the cooling response has also recently been suggested by in vivo studies in mice. The present study was thus aimed to confirm it in the isolated mouse cutaneous plantar artery. Changes in vessel diameter were measured by pressurized arteriography. Myogenic constriction was induced depending on intraluminal pressure, and was nearly abolished by the Ca2+ channel blocker nifedipine or by lowering bath temperature to 24°C. The α1-adrenoceptor agonist phenylephrine produced two-phase constriction composed of phasic and tonic components, both of which were enhanced by the cooling to 24°C. Nifedipine partly inhibited the phenylephrine constriction at 37°C, and the nifedipine-resistant constriction was further inhibited by the inositol 1,4,5-trisphosphate (IP3) receptor inhibitor xestospongin C. Although the cooling to 24°C still enhanced the phenylephrine constriction in the presence of nifedipine, the enhancement was not observed in the presence of both nifedipine and xestospongin C. In Ca2+-free solution, phenylephrine produced two-phase constriction at 37°C, which was abolished by 30-min treatment with thapsigargin, an inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA). In contrast, short-term treatment with thapsigargin for 3min rather enhanced the phenylephrine constriction in Ca2+-free solution at 37°C; however, the enhanced constriction by the cooling to 24°C was not further enhanced by the SERCA inhibitor. These results suggest that cooling inhibits Ca2+ re-uptake by SERCA, thereby enhancing constriction induced by Ca2+ released via IP3 receptors in the mouse plantar artery.