Submitted on September 16, 2003
Accepted on January 26, 2004
Presynaptic Modulation of Evoked Norepinephrine Release Contributes to Sympathetic Activation Following Pressure Overload
Wendell S. Akers1* and Lisa A. Cassis2
1 Division of Pharmacy Practice and Science, University of Kentucky, College of Pharmacy, Lexington, KY, USA
2 Division of Pharmaceutical Sciences, University of Kentucky, College of Pharmacy, Lexington, KY, USA; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY, USA
* To whom correspondence should be addressed. E-mail: wcaker0{at}uky.edu.
Activation of the sympathetic nervous system is well documented in heart failure. Our previous studies demonstrated an increase in evoked norepinephrine (NE) release from left ventricle (LV) slices at 10 days of pressure overload. The purpose of this study was to test the hypothesis that presynaptic modulation of NE release contributes to sympathetic activation following pressure overload. We examined the functional status
of the presynaptic 
2-, 
2- and AT1- receptors in LV slices from 10 day aortic constricted (AC) and sham-operated (SO) rats. Evoked [3H] overflow from LV slices preloaded with
[3H]-NE was increased in AC rats. The 2-agonist, UK14,304, decreased evoked [3H] overflow with no differences between groups. The 2-agonist, salbutamol, increased evoked [3H] overflow with greater sensitivity in slices from AC rats. The -antagonist, propranolol, decreased evoked [3H] overflow from LV slices of AC rats, but not controls. Angiotensin II (AngII) increased evoked [3H] overflow with greater sensitivity in slices from AC rats. These data support the hypothesis that aberrant presynaptic modulation of catecholamine release contributes to sympathetic activation following pressure overload.
