Lysophosphatidylcholine potentiates vascular contractile responses by enhancing vasoconstrictor-induced increase in cytosolic free Ca 2+ in rat aorta

Abstract

We investigated the effects of palmitoyl- l-α-lysophosphatidylcholine on the contractile responses of the endothelium-denuded rat aorta to high K +, noradrenaline, UK14,304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline) (a selective α 2 adrenoceptor agonist) and phorbol 12-myristate 13-acetate (PMA). Lysophosphatidylcholine at concentrations from 10 −6 M to 10 −4 M did not contract aortic strips. However, lysophosphatidylcholine strongly potentiated the UK14,304-induced contraction. High K +- and PMA-induced contractions were also potentiated. In contrast, the noradrenaline-induced contraction was only slightly potentiated by 10 −5 M lysophosphatidylcholine. In fura PE-3-loaded aortic strips, lysophosphatidylcholine (10 −5 M) markedly augmented the increase in both cytosolic free Ca 2+ ([Ca 2+] i) and contractile tension induced by UK14,304, high K + and PMA. Nicardipine (10 −7 M) and 10 −6 M Ro-31-8220 ({1-[3-(amidinothio)propyl-1H-indoyl-3-yl]-3-(1-methyl-1H-indoyl-3-yl)-maleimide-methane sulfate) strongly inhibited the increase in [Ca 2+] i and contractile tension induced by UK14,304 and in the presence of these inhibitors, the enhancing effects of lysophosphatidylcholine were attenuated. However, the enhancing effect on high K +-induced contraction was not affected by Ro-31-8220. These results suggest that lysophosphatidylcholine may cause an augmentation of the increase in [Ca 2+] i induced by UK14,304 which response is depend on protein kinase C activation and in this way potentiate contractile responses in the rat aorta. Protein kinase C independent mechanisms may also be involved in the enhancing effect of lysophosphatidylcholine on smooth muscle contraction.