Chromosomal substitution-dependent differences in cardiovascular responses to sodium pentobarbital. Anesth Analg 2006 Mar;102(3):799-805
Date
02/24/2006Pubmed ID
16492831DOI
10.1213/01.ane.0000195582.22822.e7Scopus ID
2-s2.0-33644556144 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
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 microg/mL) and small (35 microg/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.
Author List
Stekiel TA, Contney SJ, Bosnjak ZJ, Kampine JP, Roman RJ, Stekiel WJMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Chromosomes, Mammalian
Heart Rate
Male
Pentobarbital
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Species Specificity