DYSFUNCTIONAL PRESYNAPTIC ALPHA-2-ADRENOCEPTORS EXPOSE FACILITATORY BETA-2-ADRENOCEPTORS IN THE VASCULATURE OF SPONTANEOUSLY HYPERTENSIVE RATS

Previous studies on spontaneously hypertensive rats (SHR) have yielded inconsistent information about functional aberrations of the presynaptic alpha(2)- and beta(2)-adrenoceptor-mediated modulation of sympathetic neurotransmitter release. In the present investigation we studied the capacity of presynaptic beta(2)-adrenoceptors that enhance noradrenaline (NA) release in the portal vein of freely moving, unanesthetized SHR and normotensive Wistar rats (WR) using the beta(2)-selective agonist fenoterol. The results show that the presynaptic beta(2)-adrenoceptor population in SHR responds to significantly lower dosages of fenoterol than that in WR. The reason for this enhanced action, however, could not be attributed to the beta(2)-adrenoceptor itself, nor to a diminished neuronal uptake of NA, but to a diminished responsiveness of the presynaptic alpha(2)-adrenoceptor. Stimulation of presynaptic alpha(2)-adrenoceptors with oxymetazoline (45-mu-g/min) decreased basal NA levels by 46% in WR and by 3% in SHR. Blockade of alpha(2)-adrenoceptors, using 0.5 mg/kg yohimbine, induced a 4.86-fold rise in the basal NA level in WR but only a 1.89-fold rise in SHR. A subsequent dose of fenoterol, however, resulted in a further 2.5- and 2.6-fold rise in WR and SHR, respectively, indicating that there is a normal presynaptic beta(2)-adrenoceptor population in the vasculature of SHR.