Interactions of Alcohol and Prostanoids in the Vascular System

Implications for Cardiovascular Disease
  • John W. Karanian
  • Norman SalemJr.
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Epidemiologic data suggest that low alcohol consumption may protect against atherosclerosis-related cardiovascular disease, whereas high consumption is associated with vasoplastic disorders. We have examined the proposition that the capacity to produce PGs as measured in rat aorta, cerebral microvasculature (CMV), and plasma is modulated by alcohol dose and the duration of exposure and thereby contributes to changes in the vascular state. Isolated rat aorta was exposed to alcohol either in vitro or by an inhalation technique using our automated apparatus for precise control of alcohol vapor and blood concentrations (BAG). An acute exposure to moderate alcohol levels decreases the amplitude of contraction to a thromboxane mimic, whereas higher levels do not affect the response. The observed depression in aortic contractility is associated with a significant increase in the PGI2/ TxA2 ratio. This would result in a shift towards a vasodilatory/platelet antiaggregatory state in vivo. At higher levels, alcohol may act as a spasmogen, increasing intracellular Ca, and in this way may counteract the depressive effect of PGs, such as PGI2, on vascular contractility and platelet aggregability. Chronic alcohol inhalation significantly depressed aortic PG levels (moderate BAC, 27%; high BAC, 45%) and induced a mild hyperreactivity to the TxA2-mimic. This depression in PG levels may result in part from alcohol-induced depletion of 20:46; content was inversely related to the duration of exposure and decreased as much as 50%. Similarly, high BAC induced marked hypersensitivity to the pressor effects of norepinephrine and the TxA2-mimic (22% and 44%, respectively; monitored via tail artery cannula) and depressed plasma PGI2 and TxA2 levels (moderate BAC, 21%; high BAC, 37%). As expected, NSAID treatment of normal rats induced a comparable increase (48%) in vascular reactivity to the TxA2-mimic. Pretreatment of alcoholic rats with aspirin (45 mg/kg) induced a mild (5%) but insignificant increase in this response. These data are consistent with the proposition that chronic alcohol exposure has an aspirinlike effect on the prostanoid system, as reflected by altered contractility. A CMV fraction showed similar effects on PG levels; acute alcohol exposure increased the PGI2/TxA2 ratio (fourfold), and chronic exposure decreased the PGI2/TxA2 ratio (32%). One might predict that the result in vivo would be a shift towards a vasoconstrictor/platelet aggregatory state. Hyperreactivity and the depression in total PG levels associated with chronic alcohol abuse could contribute to the hypertensive and vasospastic disorders found in alcoholics. In contrast, hyporeactivity mechanism contributing to the lower incidence of atherosclerotic heart disease in this group. Thus, in response to activation of the prostanoid system, different profiles of PGs will be formed. Modification of the vascular state, at least in part, will be determined by the summation of their biological effects.


Chronic Alcohol Alcohol Exposure Inhalation Technique Blood Alcohol Level Alcohol Vapor 
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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • John W. Karanian
    • 1
  • Norman SalemJr.
    • 1
  1. 1.Section of Analytical Chemistry, Laboratory of Clinical Studies, National Institute of Alcohol Abuse and AlcoholismNational Institutes of HealthBethesdaUSA

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