Biphasic effects of exogenous phospholipase D on vessel tone.
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 phenylephrine (10(-6) M). This relaxation effects of PLD were inhibited by pretreatment of vessels with indomethacin (10(-5) M) or with N-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.
Chu
Chin-Chen
CC
Department of Anesthesiology Chi-Mei Foundation Medical Center, Taipei, Taiwan, ROC.
Loh
Shih-Hurng
SH
Chen
Ann
A
Lee
Wei-Hwa
WH
Jin
Jong-Shiaw
JS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010712:Phosphatidic Acids / Q000502:physiology; D010739:Phospholipase D / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D010712:Phosphatidic Acids; D011453:Prostaglandins; D009569:Nitric Oxide; D011433:Propranolol; D011493:Protein Kinase C; D010739:Phospholipase D