Chronic Ethanol Consumption Enhances Phenylephrine-Induced Contraction in the Isolated Rat Aorta

Abstract

Changes in reactivity to phenylephrine in aortas isolated from 2-, 6-, and 10-week ethanol-treated rats and their age-matched control and isocaloric rats were investigated. Chronic ethanol consumption enhances the contractile response of endothelium-intact and -denuded rat aortic rings to phenylephrine, a response that is time-independent. Pretreatment with indomethacin reduced E max for phenylephrine in denuded aortas from ethanol-treated rats but not control or isocaloric rats. After indomethacin treatment, no differences in E max from phenylephrine were observed among the groups.-5-heptenoic acid), an antagonist of prostaglandin H 2 /thromboxane A 2 (TXA 2 ) receptors, did not alter phenylephrine-induced contraction in control or isocaloric aortas. However, in ethanol-treated aortas, E max was reduced to control level. Moreover, phenylephrine-stimulated release of thromboxane B 2 , a stable metabolite of TXA 2 , was higher in tissues from ethanol-treated rats. Simultaneous measurement of the changes in [Ca 2ϩ ] i and contraction induced by phenylephrine showed that both parameters are higher in the rat aorta from ethanol-treated rats. CaCl 2 -induced contraction in free Ca 2ϩ solution containing phenylephrine was increased in ethanol-treated aortas. Additionally, the enhancement in CaCl 2 -induced contraction was prevented by SQ29548. The major contribution of the present study is that it demonstrates a detailed description of the mechanisms involved in the enhancement of phenylephrine-induced contraction in rat aorta from ethanol-treated rats. We provided evidence that this response was not different among the three periods of treatment employed in this study and that it is maintained by two mechanisms: an increased release of vascular smooth musclederived vasoconstrictor prostanoids (probably TXA 2 ) and an enhanced extracellular Ca 2ϩ influx.Chronic ethanol consumption is associated with cardiovascular dysfunctions independent of other known risk factors (Altura and Altura, 1982). Much of the research investigating the chronic effects of ethanol on the cardiovascular system has dealt with vascular responsiveness to vasoconstrictor agents (Strickland and Wooles, 1988;Hatton et al., 1992). Previous reports suggest that enhanced vascular reactivity to vasoconstrictor agents (Pinardi et al., 1992) or impairment of the vascular relaxation (Kahonen et al., 1999) contribute to the cardiovascular complications associated with chronic ethanol consumption.Enhanced vascular reactivity to ␣ 1 -adrenoceptor agonists was demonstrated in different arteries from ethanol-treated rats. In this line, Pinardi et al. (1992) found that chronic ethanol consumption significantly enhanced the contractile response induced by phenylephrine in aortic rings with intact endothelium. The contractile response of superior mesenteric artery to noradrenaline was shown to be greater in the rings from ethanol-treated rats (Hatton et al., 1992). Likewise, Stewart and Kennedy (1999) demonstrated an ethanol-associated increase in the m...

Ethanol Consumption Enhances Endothelin-1-Induced Contraction in the Isolated Rat Carotid

“…Much of the research on the effects of ethanol on the cardiovascular system has dealt with vascular responsiveness to vasoconstrictor agents (Strickland and Wooles, 1988;Hatton et al, 1992). Several groups have reported enhanced vascular reactivity to vasoconstrictor agents (Pinardi et al, 1992;Tirapelli et al, 2006) or impairment of the vascular relaxation (Kähönen et al, 1999) with regard to cardiovascular complications associated with ethanol consumption.…”

The impact of extracellular and intracellular Ca2+ on ethanol-induced smooth muscle contraction

“…A similar suggestion was advanced by Zhang et al [11] , who suggested that extracellular Ca 2+ is necessary for ethanol to induce contractions [11] . In addition, Tirapelli et al also suggest that the enhanced vascular response to phenylephrine in the aortas of ethanoltreated rats is maintained by an increased extracellular Ca 2+ influx [12] . The results of Walter and Messing are in line with our data [13] .…”

Vasorelaxation Effects of 2-Chloroethanol and Chloroacetaldehyde in the Isolated Rat Aortic Rings

“…25) In this study, aortic rings were pre-incubated with 2-APB, and the vasorelaxation caused by CAA were not significantly affected, either in Krebs solution or Ca 2+ -free conditions. Tirapelli 26) has found that IP 3 causes intracellular Ca 2+ release after PE treatment, which does not contribute to the response of alcohol-treated aortic rings. These may undergo PE binding to the IP 3 receptor channel and release Ca 2+ from SR and cause the aortic rings to contract.…”