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NOS Protein (no + protein)
Selected AbstractsNitric oxide synthesis and nitric oxide synthase expression in the kidney of rats treated by FK506NEPHROLOGY, Issue 1 2002LiMing WANG SUMMARY: FK506-induced nephrotoxicity is characterized by a disturbance in renal haemody-namics that is attributed to an imbalance between the various modulators of renal vascular tone. It has not been well defined whether nitric oxide (NO), as an important vasoactive factor, is involved in FK506-induced nephrotoxicity. This study was designed to evaluate the involvement of nitric oxide in FK506-induced nephrotoxicity by investigating NO synthesis and NO synthase (NOS) expression in the kidney of rats treated with FK506. Male Wistar rats weighing 240,260 g, aged 11 weeks, were administered with FK506 (3.2mg/kg per day i.m.) for 4 weeks. Renal function and urinary NOx was measured using biochemical methods at the end of both 2 and 4 weeks of treatment. Expression of NOS protein and NOS mRNA in the kidney was also investigated using Western blot analysis and reverse transcription/polymerase chain reaction, respectively. FK506 administration induced nephrotoxicity, which was indicated by renal dysfunction (elevated blood urea nitrogen and creatinine, and reduced creatinine clearance, P < 0.05 vs control). FK506-induced nephrotoxicity was accompanied by higher urinary NOx excretion at the end of 2 weeks' treatment. In parallel with an increase in NO synthesis, increased eNOS protein and mRNA expression were also found in the renal medulla and renal cortex at week 2. the expression remained at higher levels in the renal medulla and returned to normal levels in the renal cortex at week 4. FK506 treatment induced nephrotoxicity in rats, which was accompanied by a temporal increase in NO synthesis in the kidney. Increased eNOS protein and mRNA expression were also found in the kidney of treated rats, which may be responsible for the enhanced NO synthesis. [source] Morphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord. (National Medical Defense Center, Taipei, Taiwan) Br J Anaesth 2000;85:587,591.PAIN PRACTICE, Issue 2 2001Chih-Shung Wong N -Methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE10) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine-tolerant rat spinal model. Antinociceptive tolerance induced by intrathecal morphine infusion (10 ,g h,1) for 5 days. Co-administered MK801 with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [3H]MK-801 binding assays and NOS western blotting. The binding affinity of [3H]MK-801 was higher in spinal cords of morphine-related rats than in control rats. There was no difference in Bmax. Western blot analysis showed that constitutive expression of neuronal NOS protein in the morphine-tolerant group was twice that in the control group. This up-regulation was partially prevented by MK-801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord. Comment by Octavio Calvillo, M.D., Ph.D. Morphine tolerance may be due to receptor down-regulation or receptor uncoupling; activation of the NMDA-dependent pain-facilitatory system may also play a role. It has been proposed that NMDA receptor activation may play a role in morphine tolerance. NMDA receptor antagonists and nitric oxide synthase [NOS] inhibitors may prevent morphine tolerance. Tolerance was induced in rats by intrathecal injection of morphine [10 ug/h] for 5 days, co-administration of MK801 [NMDA antagonist] with morphine was used to prevent morphine tolerance. Lumbar spinal cord segments were removed and prepared for [H3]MK801 binding assays and NOS western blotting. The binding affinity of labeled MK801 was higher in spinal cords of morphine tolerant rats than in control rats. Western blot analysis showed that constitutive expression of neuronal NOS protein in the morphine tolerant rats was twice that in the control group, thus, up-regulation was prevented by MK801. The results suggest that morphine tolerance affect NMDA receptor binding activity and increase neuronal protein expression in rat the spinal cord. [source] Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafilBJU INTERNATIONAL, Issue 1 2010Serap Gur Study Type , Aetiology (case control) Level of Evidence 3b OBJECTIVE To evaluate the effect of N(G)-nitro- l -arginine methyl ester (L-NAME)-induced hypertension (HT) on erectile function in the rat and determine if the phosphodiesterase (PDE)-5 inhibitor, sildenafil, can reverse the effects of nitric oxide (NO) deficiency, as HT is a risk factor for erectile dysfunction (ED) and the NO synthase (NOS) inhibitor L-NAME induces NO-deficient HT. MATERIALS AND METHODS Thirty-six adult Sprague-Dawley male rats were divided into three groups, i.e. a control, L-NAME-HT (40 mg/rat/day in the drinking water for 4 weeks), and sildenafil-treated L-NAME-HT (1.5 mg/rat/day sildenafil, by oral gavage concomitantly with L-NAME). The erectile response expressed as a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP), evaluated after electrical stimulation of the right cavernous nerve. The isometric tension of corpus cavernosum smooth muscle (CCSM) was measured in organ-bath experiments. NOS expression was determined immunohistochemically for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein. cGMP levels were evaluated by enzyme-linked immunosorbent assay. RESULTS The erectile response was diminished in the HT group. Nitrergic and endothelium-dependent relaxation was reduced, while the relaxation response to sodium nitroprusside and contractile response to phenylephrine were not altered in CCSM from L-NAME-treated rats. HT rats showed decreased expression of nNOS, whereas eNOS and iNOS protein expression was increased. Sildenafil partly restored endothelial and molecular changes in CCSM from HT rats, but did not reverse the decreased erectile response, even as cGMP levels returned to normal levels. CONCLUSIONS Sildenafil treatment did not correct the ED in L-NAME-treated HT rats. Under sustained high blood pressure, up-regulation of PDE5 expression failed to reverse the depletion of neuronal NO and/or impaired nNOS activity. However, endothelium-dependent relaxation was restored. Drug targeting of neuronal dysfunction might delay the onset of ED in HT. [source] Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labourBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010M Cella BACKGROUND AND PURPOSE Maternal infections are one of the main causes of adverse developmental outcomes including embryonic resorption and preterm labour. In this study a mouse model of inflammation-associated preterm delivery was developed, and used to study the relationship between nitric oxide (NO) and prostaglandins (PGs). EXPERIMENTAL APPROACH The murine model of preterm labour was achieved by assaying different doses of bacterial lipopolysaccharides (LPS). Once established, it was used to analyse uterine levels of prostaglandins E2 and F2, (by radioimmunoassay), cyclooxygenases (COX) and NOS proteins (by Western blot) and NO synthase (NOS) activity. Effects of inhibitors of COX and NOS on LPS-induced preterm labour were also studied. In vitro assays with a nitric oxide donor (SNAP) were performed to analyse the modulation of prostaglandin production by NO. KEY RESULTS Lipopolysaccharide increased uterine NO and PG synthesis and induced preterm delivery. Co-administration of meloxicam, a cyclooxygenase-2 inhibitor, or aminoguanidine, an inducible NOS inhibitor, prevented LPS-induced preterm delivery and blocked the increase in PGs and NO. Notably, the levels of NO were found to determine its effect on PG synthesis; low concentrations of NO reduced PG synthesis whereas high concentrations augmented them. CONCLUSIONS AND IMPLICATIONS An infection-associated model of preterm labour showed that preterm delivery can be prevented by decreasing PG or NO production. NO was found to have a dual effect on PG synthesis depending on its concentration. These data contribute to the understanding of the interaction between NO and PGs in pregnancy and parturition, and could help to improve neonatal outcomes. [source] | ||||||||||