Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC103
Time course of vascular reactivity in hypertensive rats induced by ethanol treatment
A. Lopes da Silva1, C. Crestani2, A. Scopinho2, L. Elias1, F. Morgan2, J. Antunes-Rodrigues1, L. Resstel2
1. Physiology, Univ Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. 2. Pharmacology, Univ Sao Paulo, Ribeiro Preto, Sao Paulo, Brazil.
Several studies have shown that chronic ethanol intake is associated with cardiovascular dysfunctions, autonomic changes and hypertension. However, the mechanisms involved in ethanol intake-related blood pressure increase are not yet completely understood and can be caused by a myogenic mechanism, which involves alteration of contractile properties of vascular smooth muscle. This study evaluated basal arterial blood pressure and heart rate, as well as cardiovascular responses to infusion of vasoactive agents in unanesthetized rats maintained under chronic ethanol treatment. Male Wistar rats (250g) were treated with ethanol for 4 weeks: first week 5%, second week 10% and the last two weeks 20% of ethanol. One day before the experiments the rats were anesthetized with tribromoethanol (250 mg/kg) and a catheter (a 4-cm segment of PE-10 heat-bound to a 13-cm segment of PE-50, Clay Adams) was inserted into the abdominal aorta through the femoral artery, for blood pressure and heart rate recording. Whenever intravenous administration of drugs was necessary, a second catheter was implanted into the femoral vein. Both catheters were tunneled under the skin and exteriorized at the animal's dorsum. On the day of the experiment the animals were injected with phenylephrine (50 µg/kg/mL) or sodium nitroprusside (70 µg/kg/mL) using an infusion pump. During the treatment the animals had a progressive increase of basal values of mean arterial pressure (MAP) since one week of treatment without alteration of heart rate in basal conditions. The pressor effect of intravenous phenylephrine (Emax) was enhanced in ethanol-treated rats at all different times of treatment, when compared to respective control group. The hypotensive response to intravenous sodium nitroprusside (Emax) was enhanced in ethanol-treated rats only after the fourth week of treatment when compared to respective control group. In summary, these results indicate that ethanol chronic treatment promotes a mild hypertension that could be seen as soon as after the first week of treatment. This increase in MAP was due to the increase in both systolic and diastolic pressures. The vascular responsiveness to the pressor agent phenylephrine was enhanced since the first week of ethanol treatment, demonstrating that the system is very sensitive to pressor agents. Changes in relaxation responses are likely to be an adaptive mechanism to refrain the progressive increase of blood pressure, contributing to the mild hypertension induced by long-term exposure to ethanol. This change in relaxation could be also a response for the deficit in the nitric oxide endogenous system. These results indicate that the cardiovascular system counteracts the effects induced by chronic ethanol consumption altering mechanisms involved in the maintenance of the vascular tonus. In our study hypertension is an early event of chronic ethanol consumption.
Where applicable, experiments conform with Society ethical requirements