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Wednesday 01 December 1999

Presynaptic modulation of sympathetic neurotransmission in rat left ventricle slices: effect of pressure overload.

By: Akers WS, Cassis LA.

J Neural Transm 2000;107(8-9):885-902

The purpose of this study was to establish the rat left ventricle (LV) tissue slice system for examination of norepinephrine (NE) release from sympathetic nerve terminals. Moreover, initial experiments were performed to use the LV tissue slice system to examine differences in NE uptake and release following cardiac pressure overload induced by abdominal aortic constriction (AC). Kinetic parameters (Vmax, Km) for the specific uptake of [3H]-NE demonstrated high affinity (Km, 1.94 +/- 0.83 microM) and moderate capacity uptake (Vmax, 182 +/- 6 fmol/mg/weight/min). Following 10 days of pressure overload, the Vmax for [3H]-NE uptake was significantly reduced (by 46%) in LV slices from AC rats compared to sham-operated (SO) controls. In control rat LV slices preloaded with [3H]-NE, electrically evoked [3H]-overflow was calcium- and stimulus pulse number-dependent. The neuronal uptake inhibitor, desipramine (DMI), increased (by 60%) evoked [3H]-overflow from LV slices. The alpha2-agonist, UK14304, decreased evoked [3H]-overflow from LV slices in a concentration-dependent manner (maximal reduction of 75%). The beta2-agonist, salbutamol, increased evoked [3H]-overflow from LV slices in a concentration-dependent manner (maximal increase of 200%). In separate experiments, the LV tissue slice system was used to examine the effect of pressure overload on evoked [3H]-overflow. Following 10 days of pressure overload, evoked [3H]-overflow from LV slices of AC rats was increased (by 50%) compared to SO control. Increases in evoked [3H]-overflow from LV slices of AC rats compared to SO controls remained evident in the presence of DMI. These results demonstrate the relative importance of NE release and uptake using an in vitro LV tissue slice system. Sympathetic nerve terminals innervating rat LV were demonstrated to possess functional presynaptic alpha2- and beta2-adrenergic receptors. Finally, using this LV tissue slice system, reductions in the uptake velocity and increases in evoked NE release were demonstrated in response to acute cardiac pressure overload.

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