Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca²⁺] in Rat Mesenteric Lymphatic Vessels.

Abstract

We have demonstrated that acute alcohol intoxication (AAI) increases the magnitude of Ca(2+) transients in pumping lymphatic vessels. We tested the contribution of extracellular Ca(2+) via L-type Ca(2+) channels and intracellular Ca(2+) release from the sarcoplasmic reticulum (SR) to the AAI-induced increase in Ca(2+) transients. AAI was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats; isovolumic administration of water served as the control. Mesenteric lymphatic vessels were isolated, cannulated, and loaded with Fura-2 AM to measure changes in intracellular Ca(2+). Measurements were made at intraluminal pressures of 2, 6, and 10 cm H2O. L-type Ca(2+) channels were blocked with nifedipine; IP-3 receptors were inhibited with xestospongin C; and SR Ca(2+) release and Ca(2+) pool (Ca(2+) free APSS) were achieved using caffeine. Nifedipine reduced lymphatic Ca(2+) transient magnitude in both AAI and control groups at all pressures tested, but reduced lymphatic contraction frequency only in the control group. Xestospongin C did not significantly change any of the Ca(2+) parameters in either group; however, fractional shortening increased in the controls at low transmural pressure. RyR (ryanodine receptor) activation with caffeine resulted in a single contraction with a greater Ca(2+) transient in lymphatics from AAI than those from controls. SR Ca(2+) pool was also greater in lymphatics isolated from AAI- than from control animals. These data suggest that 1) L-type Ca(2+) channels contribute to the AAI-induced increase in lymphatic Ca(2+) transient, 2) blockage of IP-3 receptors could increase calcium sensitivity, and 3) AAI increases Ca(2+) storage in the SR in lymphatic vessels.