Submitted on November 12, 2007
Accepted on January 31, 2008
Whole body norepinephrine kinetics in angiotensin II salt hypertension in the rat
Andrew J King1, Martin Novotny2, Greg M Swain2, and Gregory D. Fink3*
1 Pharmacology and Toxicology, Michigan State University, East Lansing , Michigan, United States
2 Chemistry, Michigan State University, 48824, Michigan, United States
3 Department of Pharmacology and Toxicolo, Michigan State University, East Lansing, Michigan, United States
* To whom correspondence should be addressed. E-mail: finkg{at}msu.edu.
The purpose of this study was to investigate total body norepinephrine (NE) kinetics as an index of global sympathetic nervous system (SNS) outflow in a rat model of chronic AngII-salt hypertension. Male Sprague-Dawley rats fed a 0.4% (NS) or 2% (HS) NaCl diet were instrumented with arterial and venous catheters. After 5 recovery days and a 3 day control, AngII (150ng/kg/min) was given subcutaneously by minipump for 14 days. Plasma NE levels and total body NE spillover and clearance were determined on control day 3 and AngII infusion days 7 and 14 utilizing radioisotope dilution principles. To perform this analysis, 3H-NE and NE were measured in arterial plasma after a 90 minute infusion of tracer amounts of 3H-NE. Mean arterial pressure (MAP) was similar during control in NS and HS rats; however MAP increased to a higher level in HS rats. During the control period, plasma NE tended to be lower in rats on HS, whereas NE clearance tended to be higher in HS rats. As a result NE spillover was similar in NS and HS rats during the control period. In NS rats plasma NE, NE spillover and NE clearance were unchanged by AngII. In contrast in rats on HS plasma NE and NE spillover increased during AngII infusion, whereas NE clearance was unchanged. In conclusion, a HS diet alone or AngII infusion in animals fed NS do not affect global sympathetic outflow. However the additional hypertensive response to AngII in animals fed HS is accompanied by SNS activation.
