Phospholipase D regulates vascular smooth muscle tone in mice

Abstract

Smooth muscle tone is balanced by a number of intracellular signaling pathways which induce either relaxation or contraction. Pathways that induce contraction include activation of CaV1.2 channels by depolarization, initiation of Ca2+ release from intracellular stores, and inhibition of myosin phosphatase by Rho kinase. Here, we present evidence that phospholipase D (PLD) is involved in alpha-adrenergic-mediated contraction of vascular smooth muscle. Western blot analysis revealed the presence of PLD1 in vascular smooth muscle. In functional studies, the PLD-inhibitor butanol-1 relaxed pre-contracted aorta from wild type mice to a larger extent than the inactive congener butanol-2. The specific effect of butanol-1 was absent in the presence of the CaV1.2 channel blocker isradipine, in pre-contracted aorta from CaV1.2-deficient mice, and in pre-contracted aorta from PLD1/− mice. No specific effect of butanol-1 was observed in aorta from wild type mice being contracted by high extracellular potassium. We suggest that alpha-adrenergic contraction of vascular smooth muscle involves partially activation of PLD1 which probably maintain CaV1.2 channel activity during contraction.