Acute sinoaortic denervation induces pre- and postsynaptic alpha-adrenergic subsensitivity in mesenteric arteries in...

Bilateral sinoaortic denervation induced a rapid increase in blood pressure and heart rate in the rat. Four hours after sinoaortic denervation, the dose-response curve to l-norepinephrine (NE) in perfused mesenteric arteries in vitro was shifted to the right and the maximal response reduced, compared with sham-operated controls. These changes were abolished in the presence of cocaine (10 micrograms/ml). Four hours after sinoaortic denervation, the dose-response curves to methoxamine and serotonin, but not to adenosine-5'-triphosphate (ATP), were significantly reduced and the muscular response induced by barium chloride was not modified. Vascular responses to stimulation with different frequencies of the sympathetic nerve were reduced 4 hr after sinoaortic denervation. These changes in both the responses to l-NE and to nerve stimulation were reversed 24 hr after sinoaortic denervation. In the same preparation, 4 hr after sinoaortic denervation, the fractional release per pulse of [3H]-NE was significantly enhanced at 10 and 20 Hz frequencies of stimulation, whereas the blockade of the alpha-presynaptic receptors with phentolamine (3.1 microM) did not increase the release of [3H]-NE induced by nerve stimulation, as was observed in sham-operated controls. The results are compatible with the hypothesis that 4 hr after sinoaortic denervation, the pre- and postsynaptic alpha-adrenoceptors are desensitized. These changes could affect arterial sympathetic neurotransmission; the increase in blood pressure observed following sinoaortic denervation could therefore not be explained only by an increase in sympathetic tone.