piperidines and 1-(2-trifluoromethylphenyl)imidazole

The effect of sympathectomy on parasympathetic regulation of ocular perfusion was investigated. Uveal blood flow through the vortex veins was measured by laser Doppler flowmetry during electrical stimulation of the superior salivatory nucleus, which activates ocular parasympathetic nerves, in adult rats with intact innervation and 2 days or 6 weeks after excision of the ipsilateral superior cervical ganglion. In all groups, parasympathetic stimulation produced comparable increases in flux, which were abolished by the selective neuronal nitric-oxide synthetase inhibitor, 1-(2-trifluoromethylphenyl) imidazole. Atropine had no effect in control and acutely sympathectomized rats but abolished the flux increase in four of six chronically sympathectomized animals, and 1-(2-trifluoromethylphenyl) imidazole eliminated the residual response. The muscarinic receptor agonist bethanechol did not affect basal flow in control or sympathectomized rats. However, bethanechol enhanced parasympathetically mediated vasodilation, but only in rats studied at 6 weeks after sympathectomy, a finding consistent with the appearance of muscarinic prejunctional facilitation of nitrergic transmission. In chronically sympathectomized rats, the M(2) and M(4) receptor antagonists methoctramine and tropicamide did not affect choroidal flow during parasympathetic activation. However, pirenzepine increased flux, implying the presence of M(1) inhibitory autoreceptors on these nerves. Parasympathetically mediated increased flux was partially blocked by the M(3) antagonist 4-diphenylacetoxy-N-methylpiperdine, and the remaining vasodilation was blocked by atropine. We conclude that parasympathetic prejunctional facilitatory M(3) and probably M(5) receptors adopt a crucial role after chronic sympathectomy in maintaining nitrergic vasodilatory ocular neurotransmission in the face of down-regulated nitric oxide transmitter mechanisms.

Topics: Animals; Bethanechol; Choroid; Electric Stimulation; Enzyme Inhibitors; Female; Ganglionectomy; Imidazoles; Muscarinic Agonists; Muscarinic Antagonists; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Parasympathetic Nervous System; Piperidines; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Receptors, Presynaptic; Regional Blood Flow; Salivary Glands; Superior Cervical Ganglion; Synaptic Transmission; Time Factors