Examination of the alpha(1)-adrenoceptor signal transduction cascade in salt-sensitive hypertension.
Date of Graduation
1998
Document Type
Dissertation/Thesis
Abstract
The purpose of these studies were to identify the sites of changes in the {dollar}\\alpha\\sb1{dollar}-adrenoceptor signal transduction cascade responsible for a specific supersensitivity to norepinephrine (NE) that develops in the mesenteric arterial vascular bed from Dahl salt-sensitive rats (DS) maintained on a high salt diet (HS) for five days or three weeks as compared to Dahl salt-resistant rats (DR). Perfusion studies using the isolated perfused superior mesenteric arterial vascular bed from five day DSHS and DRHS rats and nifedipine, an L-type calcium channel blocker, were performed to assess tissue reliance on extracellular calcium for contraction. This study demonstrated that in mesenteric arterial vasculature a maximal dose of nifedipine (3 {dollar}\\mu{dollar}M), is unable to depress contractile responses to NE. These results suggest that influx of extracellular calcium through nifedipine-sensitive channels does not participate significantly in the development of NE-induced contraction and, therefore, does not participate in the development of supersensitivity in these tissues. Evaluation of basal and agonist stimulated levels of inositol 1,4,5-triphosphate (IP{dollar}\\sb3){dollar} in mesenteric arterial vasculature from Sprague-Dawley, and five day and three week DSHS and DRHS rats demonstrated the following: (1) Basal levels of IP{dollar}\\sb3{dollar} in five day and three week DSHS and DRHS were significantly elevated over those from Sprague-Dawley rats. (2) Basal levels of IP{dollar}\\sb3{dollar} in five day and three week DRHS were elevated over those from five day DSHS and were significantly elevated over those from three week DSHS. (3) NE-induced contractions of the mesenteric arterial vascular beds did not elicit changes in IP{dollar}\\sb3{dollar} levels that were different from basal levels in five day and three week DSHS and produced a significant decline in IP{dollar}\\sb3{dollar} levels in both five day and three week DRHS tissues. (3) NE-induced levels of IP{dollar}\\sb3{dollar} in mesenteric arterial vascular tissues from five day and three week DSHS were not different from their appropriate controls. These results suggest that (1) supersensitivity to NE in the superior mesenteric arterial vascular bed is not due to alterations in calcium influx through nifedipine-sensitive calcium channels and (2) basal and NE stimulated IP{dollar}\\sb3{dollar} metabolism differs between the Sprague-Dawley and Dahl strains.
Recommended Citation
Culhane, James M., "Examination of the alpha(1)-adrenoceptor signal transduction cascade in salt-sensitive hypertension." (1998). Graduate Theses, Dissertations, and Problem Reports. 8689.
https://researchrepository.wvu.edu/etd/8689