Responses of rat postganglionic sympathetic vasoconstrictor neurons following blockade of nitric oxide synthesis in vivo

Abstract

The hypothesis was tested that the activation of postganglionic sympathetic neurons contributes to the peripheral vasoconstriction and the blood pressure increase which are observed in rats after systemic blockade of nitric oxide synthase by substituted l-arginine analogues. Single and multifibre postganglionic sympathetic activity supplying hindlimb hairy skin and the activity in the caudal lumbar sympathetic trunk supplying mainly hindlimb skeletal muscle were recorded in anaesthetized, paralysed and artificially ventilated Wistar rats before, during and up to 1 h after intravenous injection of a supramaximal dose (10 or 35 mg/kg) of N G-nitro- l-arginine methyl ester. This elicited a sustained rise of arterial blood pressure, a long-lasting decrease in heart rate and vasoconstriction in hindlimb skin and skeletal muscle as measured by laser Doppler flowmetry. With intact buffer nerves all sympathetic neurons analysed responded with a decrease in their ongoing activity in parallel with the vasoconstriction and the increased blood pressure, except for one neuron which was unresponsive. These responses were probably mediated by the arterial baroreceptors, since it was shown that N G-nitro- l-arginine methyl ester did not impair the function of both the afferent and the efferent limb of the reflex. Furthermore, baroreceptor denervation almost abolished the inhibitory responses in sympathetic neurons. In baroreceptor denervated animals, with a latency of about 15 min after N G-nitro- l-arginine methyl ester there was an increase in sympathetic activity without a further increase in blood pressure. It was concluded that sympathetic vasoconstrictor neurons which supply the rat hindlimb do not contribute by neurogenic means to the vasoconstriction and the blood pressure increase occurring after blockade of the nitric oxide synthase. Instead, the results suggest that sympathetic vasoconstrictor neurons, via the baroreceptor loop, counteract the vasoconstriction caused by the blockade of endothelium-derived nitric oxide. Therefore nitric oxide does not seem to play a role in the central regulation of activity in the sympathetic vasoconstrictor pathways studied here. The long latency increase in sympathetic activity observed after N G-nitro- l-arginine methyl ester in baroreceptor-denervated animals may be due to an impairment of blood flow in the brainstem.