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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/R1262    most recent 00819.2007v1 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 Google Scholar Articles by King, A. J. Articles by Fink, G. D. PubMed PubMed Citation Articles by King, A. J. Articles by Fink, G. D.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Whole body norepinephrine kinetics in ANG II-salt hypertension in the rat

Departments of ¹Pharmacology and Toxicology and ²Chemistry, Michigan State University, East Lansing, Michigan

Submitted 12 November 2007 ; accepted in final form 31 January 2008

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 ANG II-salt hypertension. Male Sprague-Dawley rats fed a 0.4% (normal salt, NS) or 2% (HS) NaCl diet were instrumented with arterial and venous catheters. After 5 days of recovery and a 3-day control period, ANG II (150 ng·kg^–1·min^–1) 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 ANG II infusion days 7 and 14 using radioisotope dilution principles. To perform this analysis, ³H-NE and NE were measured in arterial plasma after a 90-min infusion of tracer amounts of ³H-NE. Mean arterial pressure (MAP) was similar during the control period 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 ANG II. In contrast, in rats on the HS diet, plasma NE and NE spillover increased during ANG II infusion, whereas NE clearance was unchanged. In conclusion, a HS diet alone or ANG II infusion in animals fed NS do not affect global sympathetic outflow. However, the additional hypertensive response to ANG II in animals fed HS is accompanied by SNS activation.

norepinephrine spillover; norepinephrine clearance; sympathetic nervous system; salt-sensitive hypertension