Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca 2+ ] in Rat Mesenteric Lymphatic Vessels

Abstract

Abstract

Background:

We have demonstrated that acute alcohol intoxication (AAI) increases the magnitude of Ca²⁺ transients in pumping lymphatic vessels. We tested the contribution of extracellular Ca²⁺ via L-type Ca²⁺ channels and intracellular Ca²⁺ release from the sarcoplasmic reticulum (SR) to the AAI-induced increase in Ca²⁺ transients.

Methods and Results:

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 Ca²⁺. Measurements were made at intraluminal pressures of 2, 6, and 10 cm H₂O. L-type Ca²⁺ channels were blocked with nifedipine; IP-3 receptors were inhibited with xestospongin C; and SR Ca²⁺ release and Ca²⁺ pool (Ca²⁺ free APSS) were achieved using caffeine. Nifedipine reduced lymphatic Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ transient in lymphatics from AAI than those from controls. SR Ca²⁺ pool was also greater in lymphatics isolated from AAI- than from control animals.

Conclusions:

These data suggest that 1) L-type Ca²⁺ channels contribute to the AAI-induced increase in lymphatic Ca²⁺ transient, 2) blockage of IP-3 receptors could increase calcium sensitivity, and 3) AAI increases Ca²⁺ storage in the SR in lymphatic vessels.