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 α ₂- and β₂-receptors and ANG II subtype 1 (AT ₁) 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 α ₂-agonist UK-14,304 decreased evoked ³H overflow with no differences between groups. The β₂-agonist salbutamol increased evoked ³H overflow with greater sensitivity in slices from AC rats. The β-antagonist propranolol decreased evoked ³H overflow from LV slices of AC rats but not controls. ANG II 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 after pressure overload.