Mechanisms underlying the neurogenic relaxation of isolated porcine sphincter pupillae

Mechanisms of relaxation induced by nerve stimulation were examined in isol ated porcine iris sphincter muscle in reference to norepinephrine, nitric o xide (NO) and vasoactive intestinal polypeptide (VIP) and the functional in teraction of inhibitory and excitatory nerves. Changes in isometric tension were recorded in strips of the sphincter pupillae, which were stimulated b y transmurally applied electrical pulses. The presence of neurons containin g acetylcholinesterase and tyrosine hydroxylase (TH) was determined histoch emically. Transmural electrical stimulation(0.5-20 Hz) produced a frequency -related contraction. which was reversed to a relaxation by atropine in pro staglandin F-2 alpha-contracted strips. The relaxant response was abolished by timolol and suppressed by metoprolol, a beta(1)-adrenoceptor antagonist , but was not influenced by butoxamine, a beta(2)-receptor antagonist. Nore pinephrine-induced relaxations were also attenuated only by timolol and met oprolol. Treatment with N-G-nitro-L-arginine, a NO synthase inhibitor, and [D-p-Cl-Phe(6),Leu(17)]VIP, a VIP receptor antagonist. did not inhibit the neurogenic relaxation. Contractions induced by nerve stimulation were poten tiated by timolol and physostigmine but not by the NO synthase inhibitor. I n the sphincter muscle, cholinesterase- and TH-positive nerve fibers and bu ndles were histologically detected. It is concluded that porcine iris sphin cter is innervated by cholinergic excitatory and adrenergic inhibitory nerv es. The neurogenic relaxation is associated solely with activation of beta( 1) adrenoceptors by norepinephrine but is not mediated by NO or VIP. (C) 19 99 Academic Press.