Semester

Summer

Date of Graduation

2006

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Philosophy and Humanities

Committee Chair

Matthew A Boegehold

Abstract

Study I evaluated the possibility that a HS diet can reduce the arteriolar response to muscle contraction through reduced nitric oxide (NO) availability and increased reactive oxygen species (ROS) activity. Spinotrapezius muscle arterioles were examined in rats fed a normal salt (NS; 0.45%) or high salt (HS; 4%) diets. Arteriolar diameter responses to an increase in metabolic demand were significantly less in HS rats and these HS rats exhibited increased presence of arteriolar ROS. The attenuated responses to muscle contraction in HS rats were not restored in the presence of ROS scavengers, and inhibition of NO synthesis had no effect in the HS rats.;Study II-III investigated potential mechanisms for the reduced functional dilation in HS fed rats. In study II, skeletal muscle contraction significantly increased the intensity of the hydrogen peroxide (H2O2) fluorescent marker 2',7'-dichlorofluorescein (DCFH). Arteriolar dilation and flow increases in response to muscle contraction were inhibited by the H2 O2 scavenger catalase in both groups. Exogenous H2O 2 elicited arteriolar dilation in both groups, but the magnitude of this dilation was significantly greater in the HS rats. The K+ channel inhibitors glibenclamide and tetraethylammonium (TEA) chloride reduced arteriolar dilation to exogenous H2O2 in both groups and glibenclamide reduced the functional hyperemic response.;Study III examined the effect of HS diet on arteriolar responsiveness to oxygen. Elevated superfusate oxygen resulted in arteriolar constriction and decreased flow. These responses were less in HS rats. Inhibition of 20-HETE formation with N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) and 17-octadecynoic acid (17-ODYA) reduced the oxygen-induced constriction in the NS rats, but had no effect in the HS rats. Exogenous 20-HETE elicited a concentration-dependent constriction in the NS rats that was blocked by the KCa channel inhibitor TEA and these effects were either reduced or absent in HS rats. Inhibition of ANG II-induced constriction by DDMS was significantly greater in NS than HS rats. These results suggest that H2O2 contributes to functional hyperemia but a HS diet does not effect this role, and that alterations in arteriolar oxygen sensitivity by a HS diet may contribute to the reduced functional dilation following HS intake.

Download

Share

COinS