Influence of Felodipine and Verapamil on the Sympathetic Transmitter Release and on the Pre- and Post-Junctional Effects of Exogenous Noradrenaline in the Perfused Rat Kidney:

The effects of various concentrations (0.01 to 10 µmol/L) of felodipine and verapamil on the peripheral sympathetic function were studied in perfused rat kidney preparations in vitro. Neither of these agents inhibited stimulus-induced 3H- noradrenaline (norepinephrine) release (at 0.5 and 2.0Hz). Higher concentrations of felodipine (10 µmol/L) and verapamil (1 and 10 µmol/L) significantly potentiated the transmitter release at both frequencies of stimulation. Unlike phenotolamine, felodipine 10 µmol/L enhanced the ability of exogenous noradrenaline to inhibit 3H- noradrenaline-release, indicating that this vasodilator did not antagonise prejunctional α2- receptors. The effects of verapamil 1 µmol/ L were similar to that of felodipine in this respect; however, verapamil in higher concentrations (JO µmol/L) produced slight but significant attenuation of exogenous nor adrenaline-induced inhibition of the transmitter release. Both felodipine and verapamil produced concentration-dependent inhibition of the vasoconstrictor responses to exogenous noradrenaline. It is concluded from these studies that the effects of these agents on the transmitter release may not have any clinical significance, but their ability to attenuate vascular effects of noradrenaline could contribute to their antihypertensive properties.