Effects of acute and chronic ethanol exposure on the response of rat aorta to a thromboxane mimic, U46619.
The spasmogenic properties of a stable thromboxane mimic, U46619, were determined in the isolated rat aorta after 1, 4, 8, or 12 hr of acute ethanol exposure in vitro or after 12 days of chronic exposure by inhalation. Acute ethanol exposure (87-822 mM) increased the baseline tension of aortic rings in a concentration-dependent manner. Moderate concentrations of ethanol (11 and 43 mM) decreased the maximum tensile response of rat aortic rings to U46619 after 8 and 4 hr of exposure, respectively. In contrast, higher ethanol concentrations (87 and 411 mM) did not significantly effect the maximum tensile response to U46619. Ethanol at 822 mM completely inhibited the response to U46619 and this inhibition could be 85% reversed after removal of ethanol. The inhibitory effect of 1.64 M ethanol was irreversible. Sensitivity to U46619 was inversely related to the ethanol concentration (greater than or equal to 43 mM) and incubation time. Similarly, chronic exposure to moderate blood ethanol levels (92-198 mg/100 ml) for 12 days decreased the maximum tensile response whereas high levels did not effect aortic contractility in vitro. Sensitivity of aorta from rats with mean blood ethanol levels greater than or equal to 92 mg/100 ml decreased at least one order of magnitude. The results suggest that the effect of physiologically tolerable ethanol concentrations on the amplitude of the tensile response to U46619 is biphasic both during acute exposure in vitro or following a chronic exposure period in vivo and the inhibitory effect on sensitivity for U46619 is both concentration- and time-dependent in the rat aorta preparation.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000494:pharmacology*; D013997:Time Factors
D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; D000431:Ethanol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid