Tolerance to ethanol is a complex phenomenon, with different types of tolerance resulting from different paradigms of administration of the drug. In order to study tolerance to ethanol in the cardiovascular system, two methods of chronic ethanol administration will be employed. A Pavolvian conditioning model will be used to produce environment-dependent tolerance and a liquid diet technique will be used to produce environment- independent tolerance. With the environment-dependent tolerance paradigm, various cardiovascular parameters will be assessed to determine whether or not the tolerance observed follows the conditioning pattern that has previously been observed for thermal responses. Since changes in ethanol disposition have been noted with this procedure, one aim of this proposal is to assess the possibility that the changes in ethanol disposition could be due to alterations in blood flow. The same cardiovascular parameters will be measured in environment-independent tolerant rats so that a comparison can be made. Dose response curves will be generated in each paradigm for both the amount of ethanol exposure used to generate tolerance and the amount of ethanol used to test tolerance. Thus, progressive changes and any biphasic effects of ethanol can be evaluated. Since hypertension is a common problem in alcoholics, the information obtained in these studies may shed light on the development of mechanisms of this problem.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007135-02
Application #
3110758
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1987-09-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Overall Medical
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Hariman, R J; Louie, E K; Krahmer, R L et al. (1993) Regional changes in blood flow, extracellular potassium and conduction during myocardial ischemia and reperfusion. J Am Coll Cardiol 21:798-808
Piano, M R; Holm, K; Melchior, C L et al. (1991) Alterations in splanchnic blood flow after low and high doses of ethanol. Alcohol Clin Exp Res 15:106-11
Piano, M R; Ferguson, J L; Melchior, C L (1990) Alterations in splanchnic blood flow following chronic ethanol exposure. Alcohol Clin Exp Res 14:616-22
Schrock, G D; Krahmer, R L; Ferguson, J L (1990) Coronary flow by left atrial and left ventricular microsphere injection in the rat. Am J Physiol 259:H635-8
Law, W R; Ferguson, J L (1988) Naloxone alters organ perfusion during endotoxin shock in conscious rats. Am J Physiol 255:H1106-13