Mechanisms underlying the neurogenic relaxation of isolated porcine sphincter pupillae.
Mechanisms of relaxation induced by nerve stimulation were examined in isolated porcine iris sphincter muscle in reference to norepinephrine, nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) and the functional interaction of inhibitory and excitatory nerves. Changes in isometric tension were recorded in strips of the sphincter pupillae, which were stimulated by transmurally applied electrical pulses. The presence of neurons containing acetylcholinesterase and tyrosine hydroxylase (TH) was determined histochemically. Transmural electrical stimulation (0.5-20 Hz) produced a frequency-related contraction, which was reversed to a relaxation by atropine in prostaglandin F2alpha-contracted strips. The relaxant response was abolished by timolol and suppressed by metoprolol, a beta1-adrenoceptor antagonist, but was not influenced by butoxamine, a beta2-receptor antagonist. Norepinephrine-induced relaxations were also attenuated only by timolol and metoprolol. Treatment with NG-nitro-L-arginine, a NO synthase inhibitor, and [D-p-Cl-Phe6,Leu17]VIP, a VIP receptor antagonist, did not inhibit the neurogenic relaxation. Contractions induced by nerve stimulation were potentiated by timolol and physostigmine but not by the NO synthase inhibitor. In the sphincter muscle, cholinesterase- and TH-positive nerve fibers and bundles were histologically detected. It is concluded that porcine iris sphincter is innervated by cholinergic excitatory and adrenergic inhibitory nerves. The neurogenic relaxation is associated solely with activation of beta1 adrenoceptors by norepinephrine but is not mediated by NO or VIP.
Toda
M
M
Department of Pharmacology, Shiga University of Medical Science, Seta, Ohtsu, Japan.
Okamura
T
T
Fujimiya
M
M
Azuma
I
I
Toda
N
N
D000110:Acetylcholinesterase / Q000032:analysis; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006651:Histocytochemistry; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D013566:Sympathomimetics / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D013566:Sympathomimetics; D002078:Butoxamine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase; D008790:Metoprolol; D009638:Norepinephrine