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Hitoshi Masuda

Publications and source records attributed to Hitoshi Masuda.

24 records · Page 2Linked to original sources
PubMed2002

Accumulated endogenous NOS inhibitors, decreased NOS activity, and impaired cavernosal relaxation with ischemia.

We examined whether endogenous inhibitors of nitric oxide (NO) synthesis are involved in the impaired cavernosal relaxation with ischemia in rabbits. Two weeks after cavernosal ischemia caused by partial vessel occlusion, endothelium-dependent and electrical field stimulation (EFS)-induced neurogenic NO-mediated relaxations, but not sodium nitroprusside (SNP)-induced relaxation, were significantly impaired in the isolated corpus cavernosum. The Ca(2+)-dependent NO synthase (NOS) activity and the basal and stimulated cGMP productions with carbachol or EFS were significantly decreased after ischemia. Supplementation of excess L-arginine partially recovered both of the impaired relaxations. The contents of N(G)-monomethyl-L-arginine (L-NMMA) and asymmetric N(G), N(G)-dimethyl-L-arginine (ADMA) but not L-arginine and symmetric N(G),N'(G)-dimethyl-L-arginine (SDMA) were increased in the cavernosal tissues after ischemia. Authentic L-NMMA and ADMA but not SDMA concentration dependently inhibited both relaxations without affecting the relaxation produced by SNP in the control. Excess L-arginine abolished the inhibition with L-NMMA and ADMA. These results suggest that the impaired NO-mediated cavernosal relaxations after ischemia are closely related to the decreased NOS activity and the increased accumulation of L-NMMA and ADMA.

Animals↗
PubMed2002

[Biological and pathophysiological roles of endogenous methylarginines as inhibitors of nitric oxide synthase].

Protein arginine N-methyltransferases (PRMTs) catalyse the methylation of guanidinonitrogen(s) of arginine to produce NG-monomethyl-L-arginine (L-NMMA), asymmetric NG,NG-dimethyl-L-arginine (ADMA) and symmetric NG,NG-dimethyl-L-arginine (SDMA), which are subsequently released into the cytoplasm following proteolysis. Free intracellular L-NMMA and ADMA, but not SDMA, are inhibitors of all three isoforms of nitric oxide synthases (nNOS, eNOS and iNOS). L-NMMA and ADMA, but not SDMA, are actively metabolized by dimethylarginine dimethylaminohydrolase (DDAH) to L-citrulline and methylamine (and dimethylamine). Free methylarginines are detectable in cell cytosol, plasma and tissues. Elevated ADMA has been detected in the plasma of patients or experimental animals with hypercholesterolemia, renal failure, atherosclerosis, hypertension, thrombotic microangiopathy, peripheral arterial occlusive disease and in the regenerated endothelial cells after angioplasty. Moreover, in the non-cardiovascular field, ADMA was increased in the urethral tissue following ischemia and in the plasma of patients with schizophrenia and multiple sclerosis. Altered biosynthesis of NO has been implicated in the pathogenesis of these diseases, and it is possible to consider that the accumulation of endogenous L-NMMA and ADMA underlies the impaired NO generation and increased O2- production. We described herein the biosynthesis, transmembrane transport, metabolic pathway and possible pathophysiological roles of endogenous methylarginines.

Animals↗
PubMed2002

[A comparative study assessing clinical effects of naftopidil and tamsulosin hydrochloride on benign prostatic hyperplasia].

We compared the efficacy of naftopidil with that of tamsulosin hydrochloride for benign prostatic hyperplasia patients. Eighty-five patients without improvement of quality of life (QOL) score by the administration of 50-75 mg naftopidil for more than four weeks were assigned to receive doses of 0.1-0.2 mg tamsulosin hydrochloride and 89 patients without improvement of QOL score by the administration of 0.1-0.2 mg tamsulosin hydrochloride for more than four weeks were assigned to receive doses of 50-75 mg naftopidil once a day for 8 weeks. International prostate symptom score, maximum flow rate, residual urine volume and side effect profile were determined before the administration of the first medicine, before the administration of the second medicine and after 8 weeks of treatment with the second medicine. In the group without improvement of QOL score by naftopidil, significant improvements in symptoms of urgency, weak stream and straining were observed after 8 weeks of treatment with tamsulosin hydrochloride. In the group without improvement of QOL score by tamsulosin hydrochloride, significant improvements in symptoms of incomplete emptying, intermittency and nocturia were observed after 8 weeks of treatment with naftopidil. In conclusion, improvement of symptoms by each alpha 1-blocker differs symptom by symptom. Tamsulosin hydrochloride was superior to naftopidil for the symptoms of urine flow and naftopidil was superior to tamsulosin hydrochloride for the symptom of nocturia.

Adrenergic alpha-Antagonists↗
PubMed2002

Localization and role of nitric oxide synthase and endogenous nitric oxide synthase inhibitors in the rabbit lower urinary tract.

PURPOSE: We investigated the possible role of endogenous methylarginine derivatives, such as NG-monomethyl-L-arginine (L-NMMA), asymmetrical NG, NG-dimethyl-L-arginine (ADMA) and symmetrical NG, N'G-dimethyl-L-arginine (SDMA), for regulating nitric oxide synthase in the rabbit lower urinary tract. MATERIALS AND METHODS: Strips of detrusor, trigone and proximal urethra were processed for the determination of endogenous methylarginines and L-arginine by automated high performance liquid chromatography. We also compared nitric oxide synthase activity and nitric oxide mediated functional responses to electrical field stimulation in the 3 regions. Nitric oxide synthase activity was measured by determining the conversion of [3H] L-arginine to [3H] L-citrulline. RESULTS: L-NMMA, ADMA and SDMA were detectable by high performance liquid chromatography in the detrusor, trigone and proximal urethra. Electrical field stimulation induced nitric oxide mediated prominent relaxation in the trigone and proximal urethra, while no relaxation response was observed in the detrusor. Exogenously applied 1 to 100 microM. L-NMMA and 1 to 100 microM. ADMA but not 100 microM. SDMA dependently inhibited Ca2+ dependent nitric oxide synthase activity in all regions, and electrical field stimulation induced relaxation in the trigone and proximal urethra. Inhibition with L-NMMA and ADMA was blocked in the presence of 3 mM. L-arginine but not by 3 mM. D-arginine. CONCLUSIONS: Three methylarginines and nitric oxide synthase are localized throughout the rabbit lower urinary tract. Endogenous L-NMMA and ADMA may be involved in regulating nitric oxide biosynthesis of the micturition reflex in the normal or disease state.

Animals↗
PubMed2002

Changed responsiveness of the detrusor in rabbits with alloxan induced hyperglycemia: possible role of 5-hydroxytryptamine for diabetic bladder dysfunction.

PURPOSE: We assessed whether the responsiveness of the detrusor is changed in rabbits with alloxan induced hyperglycemia. MATERIALS AND METHODS: Hyperglycemia was induced by a bolus intravenous injection of alloxan (60 mg./kg.) in Japanese White male rabbits. At 16 weeks after alloxan detrusor muscle strips prepared from age matched normoglycemic and hyperglycemic rabbits were mounted in organ chambers. Contractile responses to KCl, carbachol, adenosine triphosphate, 5-hydroxytryptamine and electrical field stimulation were compared in the 2 groups. The effect of sarpogrelate as a selective antagonist of 5-hydroxytryptamine 2A receptor on the contractile response to 5-hydroxytryptamine was also compared. RESULTS: The current experiments demonstrated that hyperglycemia caused significant decreases in neurogenic and carbachol induced contractions accompanied by unchanged adenosine triphosphate and KCl induced contractions. Neurogenic bladder contraction in the hyperglycemic rabbit was significantly potentiated by exogenously applied 5-hydroxytryptamine. Potentiation was detectable even after the desensitization of purinoceptors but undetectable in the presence of atropine. Hyperglycemia resulted in enhancement of the 5-hydroxytryptamine induced bladder contraction. Sarpogrelate tended to normalize the enhanced contraction. CONCLUSIONS: The decrease in neurogenic bladder contraction possibly accompanied by the decreased density of muscarinic receptors, the potentiation of neurogenic bladder contraction with 5-hydroxytryptamine probably due to facilitated cholinergic transmission and the enhanced contractility to 5-hydroxytryptamine would be at least in part involved in bladder dysfunction associated with hyperglycemia.

Animals↗