Biomedical subjects

Tomio Okamura

Publications and source records attributed to Tomio Okamura.

7 recordsLinked to original sources

PubMed2002

Mechanisms underlying endothelium-dependent, nitric oxide- and prostanoid-independent relaxation in monkey and dog coronary arteries.

We compared the mechanisms of vasorelaxation of acetylcholine and of substance P with reference to K(+) channels, and analyzed pharmacologically the nature of endothelium-derived substance(s) other than NO and prostanoids in monkey and dog coronary arteries. Coronary arteries were isolated from monkeys and dogs, and the isometric tension of the artery strips was measured. In canine coronary artery strips treated with indomethacin plus N(G)-nitro- L-arginine ( L-NA) and partially contracted with prostaglandin F(2alpha), acetylcholine induced concentration-related relaxation, which was abolished by removal of the endothelium. The relaxation was markedly suppressed but not abolished in the strips exposed to high K(+) media. Charybdotoxin plus apamin potently inhibited the relaxation to the similar extent to that by high K(+) media, whereas glibenclamide or iberiotoxin had no effect. The relaxation was markedly inhibited by quinacrine, a phospholipase A(2) inhibitor, and ketoconazole, a selective cytochrome P450 (CYP) 3A inhibitor, but not by sulfaphenazole, a selective CYP 2C inhibitor. In contrast to acetylcholine, endothelium-dependent and indomethacin-plus- L-NA-resistant relaxation induced by substance P was not inhibited by high K(+) media, charybdotoxin plus apamin, or ketoconazole. Quinacrine and AA861, a 5-lipoxygenase inhibitor, inhibited the relaxation induced by substance P. In monkey coronary artery, acetylcholine-induced relaxation resistant to indomethacin plus L-NA was abolished by endothelial denudation and by treatment with high K(+) media, charybdotoxin plus apamin, progesterone and ketoconazole, but was not affected by iberiotoxin or sulfaphenazole. Substance P did not relax monkey coronary arteries. It is concluded that endothelium-dependent, nitric oxide- and prostanoid-independent relaxation induced by acetylcholine in monkey and dog coronary arteries are mediated by charybdotoxin plus apamin-sensitive but iberiotoxin-insensitive Ca(2+)-activated K(+) channel opening substance(s), which may be CYP3A-derived arachidonic acid metabolite(s). Contrasting to the response to acetylcholine, endothelium-dependent, indomethacin-plus- L-NA-resistant relaxation induced by substance P in dog coronary artery is not associated with K(+) channel opening, and may be mediated by 5-lipoxygenase product(s).

Acetylcholine↗

PubMed2002

Endothelial and neuronal functions in cerebral and temporal arteries from monkeys fed a high-cholesterol diet.

Modifications by hyperlipidemia of endothelium-dependent and -independent relaxations were evaluated in cerebral and temporal arteries from control and hyperlipidemic (high cholesterol-fed) monkeys. Histologically atherosclerotic lesions were not observed in either group. Relaxations induced by histamine, abolished by N(G)-nitro->L-arginine (>L-NA), were significantly potentiated in the hyperlipidemic monkey cerebral arteries, compared with those in the arteries from control monkeys. Treatment with superoxide dismutase did not affect the histamine-induced relaxation. Conversely, endothelium-dependent relaxations induced by A23187, Ca2+ ionophore, in cerebral arteries did not differ between control and hyperlipidemic monkeys. In temporal arteries, relaxations by acetylcholine and A23187 did not differ between control and hyperlipidemic monkeys. Endothelium-dependent and -independent relaxations by adenosine diphosphate in cerebral and temporal arteries were not affected by hyperlipidemia. Endothelium-independent relaxations by exogenously applied nitric oxide did not differ in the arteries from control and hyperlipidemic monkeys. Nicotine-induced relaxations in cerebral arteries, which were mediated with nitric oxide released from nitroxidergic (nitrergic) nerves, and the contractions caused by nicotine in temporal and mesenteric arteries treated with >L-NA did not differ between control and hyperlipidemic monkeys. It is concluded that long exposure to hyperlipidemia did not affect endothelial functions of monkey middle cerebral and temporal arteries but enhanced nitric oxide-mediated relaxations caused by histamine, possibly due to upregulation of endothelial histamine receptor-mediated functions in the cerebral arteries. The nitroxidergic (nitrergic) and adrenergic nerve functions do not seem to be affected by hyperlipidemia.

Animals↗

PubMed2002

Effects of nipradilol on alpha-adrenoceptor function in ocular arteries.

The effects of nipradilol, a drug used in the treatment of glaucoma, on the contractions induced by noradrenaline and phenylephrine in isolated dog central retinal, external and internal ophthalmic arteries and pig ciliary arteries were investigated. In dog ocular arteries treated with oxyhemoglobin (1.6 x 10(-5) mol/l) to adsorb nitric oxide, noradrenaline (2 x 10(-8) to 10(-5) mol/l) produced a concentration-related contraction which was markedly inhibited by prazosin but not by yohimbine. Nipradilol (10(-9) to 10(-7) mol/l) slightly but significantly inhibited the noradrenaline-induced contraction in a concentration-related manner, but the inhibitory potency and efficacy were much less than those of prazosin. However, nipradilol inhibited the phenylephrine-induced contraction with a similar PA(2) value of prazosin. In pig ciliary arteries treated with oxyhemoglobin, noradrenaline-induced contraction was slightly inhibited by prazosin but markedly inhibited by yohimbine. Nipradilol, similarly to timolol, did not inhibit, but rather tended to potentiate, the contraction elicited by noradrenaline. The contraction induced by phenylephrine was significantly inhibited by prazosin and nipradilol. It is concluded that nipradilol acts as an alpha(1)-adrenoceptor antagonist (but not as an alpha(2)-adrenoceptor antagonist) in the ocular arteries, which may partially explain its ocular-pressure-lowering mechanism. Taken together with the results of our previous studies, the potencies of the nipradilol-induced vascular actions in ocular arteries are found to be in the following order: beta-adrenoceptor inhibition > alpha(1)-adrenoceptor inhibition falling dots direct vasodilation via a release of nitric oxide.

Adrenergic alpha-Antagonists↗

PubMed2002

[Nitroxidergic (nitrergic) nerve and erectile dysfunction].

In vascular tissues including the corpus cavernosum, the organ function is reciprocally regulated by noradrenergic and non-adrenergic, non-cholinergic (NANC) nerves. NANC nerves innervating the corpus cavernosum is thought to be nitroxidergic (nitrergic) nerves which liberate nitric oxide (NO) produced by neuronal NO synthase, and liberated NO activates soluble guanylate cyclase (sGC) in cavernous smooth muscle cells. Intracellular increase in cyclic (c) GMP by activation of sGC dilates cavernous smooth muscle and then induces penile erection. Nitroxidergic (nitrergic) vasodilator nerves also innervate cavernous arteries and veins which regulate the blood volume in the corpus cavernosum. The order of potency of nitroxidergic nerve functions in these tissues (cavernosum > artery >> vein) may be suitable for producing the erection. Therefore, obstruction of the arteries and impairment of nitroxidergic (nitrergic) nerve function are speculated to be one of the causes for erectile dysfunction (ED). On the other hand, NO derived from the cavernous endothelium may partly contribute to erectile function. Sildenafil (Viagra) is one of the potent therapeutics for ED. The agent is a selective phosphodiesterase type 5 (PDE-V) inhibitor that inhibits degradation of cGMP elevated by NO mainly derived from the nerves. To develop more selective and safer therapeutics for ED, further systematic investigations are required.

Animals↗

PubMed2002

Neurogenic cerebral vasodilation mediated by nitric oxide.

In cerebral arteries isolated from most of mammals, nerve stimulation produces relaxations in contrast to contractions in peripheral arteries. The relaxant mechanism is found to be non-adrenergic and non-cholinergic, but the neurotransmitter is not clarified until recently. Based on several functional and histological studies with isolated cerebral arteries, nitric oxide (NO) is now considered to be a neurotransmitter of the vasodilator nerve and the nerve has been called a nitroxidergic (nitrergic) nerve. Upon neural excitation, calcium influxed through N-type Ca2+ channels activates neuronal NO synthase, and then NO is produced by the enzyme from L-arginine. The released NO activates soluble guanylate cyclase in smooth muscle cells, resulting in relaxation with a cyclic GMP-dependent mechanism. The functional role and neuronal pathway have also been investigated in anesthetized dogs and Japanese monkeys. The nitroxidergic (nitrergic) nerves innervating the circulus arteriosus, including the anterior and middle cerebral and posterior communicating arteries, are found to be postganglionic nerves originated from the ipsilateral pterygopalatine ganglion and tonically dilate cerebral arteries in the resting condition. Our findings suggest that the nitroxidergic (nitrergic) nerve plays a physiologically important role to maintain a steady blood supply to the brain.

Animals↗

PubMed2002

Functional study on nitroxidergic nerve in isolated dog pulmonary arteries and veins.

In dog pulmonary arterial and venous strips without endothelium under treatment with prazosin, nicotine induced relaxation that was abolished by N(G)-nitro-L-arginine, hexamethonium and methylene blue. L-Arginine antagonized the N(G)-nitro-L-arginine action. Neurogenic relaxations tended to be more evident in the vein. Nitric oxide (NO)-induced relaxations were greater in the veins than in the arteries. Concentrations of NO to induce the same magnitude of relaxation as that to nicotine were higher in the arteries. In conclusion, dog pulmonary arteries and veins are innervated by nitroxidergic (nitrergic) nerves, and NO is released by nerve stimulation with nicotine in a larger amount in the artery than the vein.

Animals↗

PubMedDate not supplied

Comparison of the responses to thrombin in monkey renal and uterine arteries.

OBJECTIVE: Thrombin is known to regulate vascular tone. We analyzed and compared mechanisms of thrombin action in primate renal and uterine arteries. METHODS: Isolated Japanese monkey renal and uterine arteries were suspended in Ringer-Locke solution for tension recordings. RESULTS: Renal arteries responded to thrombin with relaxation, which was inhibited by N(G)-nitro-L-arginine or indomethacin and reversed to contractions by the combination. The relaxations were also reversed to contractions by endothelial denudation. Conversely, thrombin caused uterine arterial contractions that were unaffected by endothelial denudation. Relaxations in both renal arteries and contractions in uterine arteries were suppressed by hirudin (a specific thrombin inhibitor). Relaxant responses to A23187 (Ca(2+) ionophore), nitroprusside sodium (nitric oxide donor), and beraprost sodium (prostacyclin analogue) did not differ between renal and uterine arteries. CONCLUSION: Thrombin-induced relaxation of renal arteries appears to be mediated by nitric oxide and vasodilator prostaglandins liberated from the endothelium, whereas uterine arterial contraction is caused by an endothelium-independent mechanism.

Animals↗