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Anesth Analg 2006;102:799-805
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000195582.22822.e7

ANESTHETIC PHARMACOLOGY

Chromosomal Substitution-Dependent Differences in Cardiovascular Responses to Sodium Pentobarbital

Thomas A. Stekiel, MD, Stephen J. Contney, MS, Zeljko J. Bosnjak, PhD, John P. Kampine, MD, PhD, Richard J. Roman, PhD, and William J. Stekiel, PhD

Departments of Anesthesiology and Physiology, Medical College of Wisconsin, Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin

Address correspondence and reprint requests to Thomas A. Stekiel, MD, Anesthesia Research, M4280, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226. Address e-mail to tstekiel{at}mcw.edu.

In this study we addressed initial laboratory observations of enhanced cardiovascular sensitivity to sodium pentobarbital (PTB) in normotensive Dahl Salt Sensitive rats (SS) compared to Brown Norway (BN) rats. We also used unique consomic (chromosomal substitution) strains to confirm preliminary observations that such differences were related to chromosome 13. Increasing concentrations of PTB were administered sequentially to SS, BN, and SS strains with BN chromosomal substitutions until the point of cardiovascular collapse. Both spontaneous and controlled ventilation were studied. The effect of large (450 µg/mL) and small (35 µg/mL) concentrations of PTB on in situ transmembrane potential of mesenteric arterial vascular smooth muscle (VSM) cells was also measured in these animals with local sympathetic innervation both intact and eliminated. An analysis of variance was used to identify significant differences among groups. Despite virtually identical plasma clearance of PTB, cardiovascular collapse occurred at approximately 35%–45% smaller cumulative doses of administered PTB in SS and other strains compared with BN and SS.13BN (introgression of BN chromosome 13 into an SS) in both spontaneous and controlled ventilation. In neurally intact preparations, large dose PTB-induced VSM hyperpolarization was 4–5 times greater than the small dose in SS and SS.16BN but not in BN and SS.13BN strains. Denervation eliminated this strain difference. These results suggest that enhanced cardiovascular sensitivity to PTB in SS rats is related to greater hyperpolarization of VSM transmembrane potential in resistance vessels and this effect is associated with chromosome 13.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.