YOSHIDA Kazuhide Shiga University of Medical Science Pharmacology, Assistant, 医学部, 助手 (00210683)
AYAJIKI Kazuhide Shiga University of Medical Science Pharmacology, Assistant, 医学部, 助手 (10167968)
OKAMURA Tomio Shiga University of Medical Science Pharmacology, Associate Professor, 医学部, 助教授 (70152337)
|Budget Amount *help
¥7,900,000 (Direct Cost : ¥7,900,000)
Fiscal Year 1997 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1996 : ¥4,900,000 (Direct Cost : ¥4,900,000)
Original findings on vascular nitroxidergic innervation obtained in 1996 and 1997 by a financial support from Japanese Government are as follows.
I)Cerebral artery. Relaxations and increments in cyclic GMP induced by nitroxidergic nerve stimulation in canine cerebral arteries were selectively inhibited by inhibitors of Ca/calmodulin-dependent proteinkinase II,suggesting that the protein phosphorylation is involved in the activation of nitric oxide (NO) synthase in nerve terminals. NO-mediated relaxations by nerve stimulation of monkey cerebral arteries were attenuated by acetylcholine and eserine, a cholinesterase inhibitor, and potentiated by atropine, indicating that neurogenic acetylcholine interferes with the synthesis and/or release of NO from the nerve. Prejunctional muscarinic receptor subtype involved appears to be M_2. Nitroxidergic nerve function was impaired by hypoxia, possibly due to modulation of intracellular pH,and by flunarizine that blocks the Ca influx in nerve termin
als, thus reducing the NO synthesis. On the basis of pharmacological study in isolated canine cerebral arteries, potentiation of nitroxidergic nerve function was suggested to be involved partially in hypercapnia-induced cerebral vasodilatation.
II)Corpus cavernosum. Canine cavernous strips responded to transmural electrical stimulation with relaxations which were abolished by NO synthase inhibitors and restored by L-arginine. Atropine and VIP antagonist were ineffective. In anesthetized dogs, electrical stimulation of pelvic nerve plexus increased the intracavernous pressure and provoked penile erection, the effects being abolished by intravenous and intracavernous injections of NO synthase inhibitors. Hexamethonium abolished the response to nerve stimulation, suggesting the presence of nitroxidergic ganglion in the vicinity of corpus. The findings indicate that the nitroxidergic nerve plays a crucial role in penile erection.
III)Peripheral arteries. In ciliary and retinal arteries from monkeys and dogs and lingual arteries from monkeys, evidences for nitroxidergic vasodilator nerves, together with adrenergic vasoconstrictor, were provided by pharmacological and histochemical studies. Our data indicate that NO and CGRP play a role as vasodilator mediators in canine skin arteries.
IV)Blood pressure. In anesthetized monkeys, intravenous N^G-nitro-L-arginine, a NO synthase inhibitor, raised systemic blood pressure, and L-arginine reversed the effect. The pressor action of the inhibitor was reduced by ganglionic blockade but not by treatment with phentolamine, suggesting that NO liberated from vasodilator nerves under resting conditions contributes to decreased vascular resistance. Less