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This Article Full Text Full Text (PDF) All Versions of this Article: 289/1/H188    most recent 00504.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Drenjancevic-Peric, I. Articles by Lombard, J. H. Search for Related Content PubMed PubMed Citation Articles by Drenjancevic-Peric, I. Articles by Lombard, J. H.

Restoration of normal vascular relaxation mechanisms in cerebral arteries by chromosomal substitution in consomic SS.13^BN rats

¹Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and ²Department of Biochemistry, University of Texas, Southwestern Medical Center, Dallas, Texas

Submitted 4 June 2004 ; accepted in final form 10 March 2005

This study sought to identify the mechanisms of vascular relaxation that are rescued in middle cerebral arteries (MCA) of SS.13^BN consomic rats by substituting chromosome 13 containing the renin gene from Brown Norway (BN) rats into the Dahl salt-sensitive (SS) genetic background. Isolated MCA from SS rats exhibited an indomethacin-sensitive constriction in response to acetylcholine (ACh) and hypoxia. ACh-induced dilation was NO dependent and hypoxic dilations were cyclooxygenase (COX) dependent in BN and SS.13^BN rats. In SS rats, hypoxic dilation was restored by indomethacin and abolished by inhibiting cytochrome P-450 epoxygenases, suggesting a role for epoxyeicosatrienoic acids. MCA from SS and SS.13^BN rats constricted and MCA from BN rats dilated in response to the stable prostacyclin analog iloprost. MCA from SS.13^BN and BN rats (but not SS rats) dilated in response to the prostaglandin E₂ receptor agonist butaprost. Hypoxia increased prostacyclin release in cerebral arteries from all the strains, whereas thromboxane A₂ production was reduced in BN rat vessels only. These data suggest that SS rats may be less sensitive to vasodilator prostaglandins and that normalization of renin-angiotensin system regulation causes a switch from production of COX-derived vasoconstrictor metabolites (in SS rats) toward NO-dependent relaxation in response to ACh- and prostaglandin-dependent dilation in response to hypoxia in SS.13^BN rats.

angiotensin II; vasodilation; hypoxia; endothelium; genetic models; physiological genomics; vascular relaxation

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				M. P. Kunert, M. R. Dwinell, I. Drenjancevic Peric, and J. H. Lombard Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS x BN cross Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R516 - R527. [Abstract] [Full Text] [PDF]

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