Biphasic Effects of Exogenous Phospholipase D on Vessel Tone

Chin-Chen Chu；Shih-Hurng Lob；Ann Chen；Wei-Hwa Lee；Jong-Shiaw Jin

phospholipase D ； nitric oxide ； prostaglandin ； protein kinase C ； vascular smooth muscle

The Chinese Journal of Physiology

45卷1期（2002 / 03 / 01）

1 - 7

英文

There exists functional significance for agonists stimulated phospholipase D (PLD) and exogenous PLD in different systems, but the functional importance of PLD on vessel tone is not clear. We studied the functional importance of PLD in whole animals and in isolated vessel preparation. In in vivo study, we demonstrated that intravenous injection of PLD at 10,30, and 100 units to male Sprague-Dawley rats did not significantly alter the mean arterial blood pressure and heart rate in 30 minutes. However, in a denuded vessel preparation, PLD from 10^(-3) units/ml to 10 units/ml induced vasoconstriction from 2.8±1.7 % to 30.5±1.7 % of maximal KCI contraction in calcium enriched physiological salt solution (PSS). This vasoconstrictive effects of PLD were significantly inhibited by omission of extracellular calcium from PSS or by pretreatment the vessels with nifedipine (10^(-6) M). Pretreated the denuded vessels with a protein kinase C inhibitor, chelerythrine (10^(-6)M), did not significantly alter the vasoconstrictive effects of PLD. These results indicate that calcium channel rather than protein kinase C activation is involved in PLD-induced vasoconstriction. In endothelium-intact vessels, application of PLD from 10^(-4) units/ml to 10 units/ml induced endothelium dependent relaxation in vessels precontracted with phenylepbrine (10^(-6) M). This relaxation effects of PLD were inhibited by pretreatment of vessels with indomethacin (10^(-5) M) or with N(superscript ∞)-nitro-L-arginine (L-NAME, 10^(-4) M), suggesting prostaglandin and nitric oxide released by PLD stimulation. The biphasic effects of PLD on vessel tone are mediated by extracellular calcium and by endothelium-derived nitric oxide and prostaglandin.

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