Presynaptic modulation of evoked NE release contributes to sympathetic activation after pressure overload.
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 after pressure overload. We examined the functional status of the presynaptic alpha(2)- and beta(2)-receptors and ANG II subtype 1 (AT(1)) receptors in LV slices from 10-day aortic constricted (AC) and sham-operated (SO) rats. Evoked (3)H overflow from LV slices preloaded with [(3)H]NE was increased in AC rats. The alpha(2)-agonist UK-14,304 decreased evoked (3)H overflow with no differences between groups. The beta(2)-agonist salbutamol increased evoked (3)H overflow with greater sensitivity in slices from AC rats. The beta-antagonist propranolol decreased evoked (3)H overflow from LV slices of AC rats but not controls. ANG II increased evoked (3)H 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 after pressure overload.
Akers
Wendell S
WS
Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, 800 Rose St., Rm. 231B, Lexington, KY 40536-0082, USA. wcaker0@uky.edu
Cassis
Lisa A
LA
D000320:Adrenergic Fibers / Q000378:metabolism; D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology; D004195:Disease Models, Animal; D006321:Heart / Q000294:innervation; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
D044140:Receptor, Angiotensin, Type 1; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; D009638:Norepinephrine