Involvement of nitric oxide and cyclic GMP in rabbit urethral relaxation

Dokita, Shinobu; Smith, Shannon D.; Nishimoto, Tadashi; Wheeler, Marcia A.; Weiß, Robert M.

doi:10.1016/0922-4106(94)90136-8

Cited by 54 publications

(33 citation statements)

References 23 publications

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“…Dokita et al [22] also reported that zaprinast, a phosphodiesterase-5 inhibitor, potentiated urethral relaxation in rabbits. NO is an important mediator in the relaxation of isolated bladder and urethral smooth muscle [21,23]; NO also modulates prostatic smooth muscle tone [24]. Thus, increased NO activity after resuming normal sexual activity may have been responsible for the improvement in LUTS in the present study.…”

Section: Discussionmentioning

confidence: 61%

Sildenafil influences lower urinary tract symptoms

Krishnamurthy¹,

Kulinskaya²,

McNicholas³

et al. 2002

BJU International

230

135

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Objective To assess the possible relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in men, and whether treatment of their ED with sildenafil influences their LUTS. Patients and methods In all, 112 men with ED attending the andrology outpatient clinic were offered oral sildenafil and reviewed 1 and 3 months after treatment. They completed the International Index of Erectile Function and the International Prostate Symptom Score (IPSS) questionnaires at baseline and each review. Scores were designated to indicate the visit number and differences between the visits calculated. Results A third of the men had an initial IPSS of > 7; there was no relationship between baseline urinary and sexual function scores. After treatment with sildenafil, the urinary scores at 3 months correlated strongly with the sexual function scores. There was a significant inverse relationship between the baseline IPSS and sexual function scores after treatment. The overall trend in the IPSS was towards improvement after treatment with sildenafil. Conclusions In men with ED there is no relationship between sexual function scores and urinary symptom scores before treating ED. Treatment with sildenafil appears to improve urinary symptom scores. A lower IPSS at baseline appears to predict a better response to ED therapy with sildenafil.

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Section: Discussionmentioning

confidence: 61%

Sildenafil influences lower urinary tract symptoms

Krishnamurthy¹,

Kulinskaya²,

McNicholas³

et al. 2002

BJU International

230

135

View full text Add to dashboard Cite

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“…Also, Dokita et al (1994), in the rabbit urethra, described higher NOS activity present in the particulate fraction than in the soluble one, which was Ca2"-independent and inhibited by L-canavanine > L-NMMA>L-NOARG. A similar Ca2+ -independant enzyme (also inhibited more by L-canavanine than by L-NMMA or L-NOARG) was measured in infected urine pellets reflecting the activity of an inducible isoform (iNOS) in inflammatory cells .…”

Section: Discussionmentioning

confidence: 90%

“…Furthermore, functional studies have demonstrated that isolated urethral and trigonal smooth muscles in all the species studied so far, respond to electrical field stimulation (EFS) with pronounced NANC relaxations, which can be blocked by NO synthesis inhibitors and mimicked by NO and NO donors (Garcia-Pascual et al, 1991;Andersson et al, 1991;Persson et al, 1992;1993;Garcia-Pascual & Triguero, 1994). This suggests that NO, or a related compound, is the relaxant mediator, which acts by increasing guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in smooth muscle (Garcia-Pascual & Triguero, 1994;Dokita et al, 1994). Moreover, an increase in both nitrite and nitrate, the metabolites of NO, has been measured in human urethral preparations upon EFS, which was inhibited by N0-nitro-L-arginine methyl ester (L-NAME) (Leone et al, 1994).…”

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confidence: 99%

Characterization of nitric oxide synthase activity in sheep urinary tract: functional implications

Garcia-Pascual

Costa

Labadía

et al. 1996

British J Pharmacology

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1 To define further the role of nitric oxide (NO) in urinary tract function, we have measured the presence of nitric oxide synthase (NOS) activity, and its relationship with functional NO-mediated responses to electrical field stimulation (EFS) in the urethra, the detrusor and the ureter from sheep. NOS activity was assayed by the conversion of L-['4C]-arginine to L-['4C]-citrulline. Endogenous production of citrulline was confirmed by thin layer chromatography. 2 NOS enzymatic activity was detected in the cytosolic fraction from tissue homogenates with the following regional distribution (pmol citrulline mg-' protein min-'): urethra (33 + 3.3), detrusor (13.1 + 1.1) and ureter (1.5 + 0.2). No activity was detected in the particulate fraction of any region. 3 NOS activity was dependent on Ca2+-calmodulin and required exogenously added NADPH and tetrahydrobyopterin (BH4) for maximal activity. Exclusion of calmodulin from the incubation mixture did not modify NOS activity, but it was significantly reduced in the presence of the calmodulin antagonist, calmidazolium, suggesting the presence of enough endogenous calmodulin to sustain the observed NOS activity. 4 NOS activity was inhibited to a greater extent by NG-nitro-L-arginine (L-NOARG) and its methyl ester (L-NAME) than by NG-monomethyl-L-arginine (L-NMMA), while 7-nitroindazole (7-NI) was a weak inhibitor and L-cannavine had no effect. 5 Citrulline formation could be inhibited by superoxide dismutase in an oxyhaemoglobin-sensitive manner, suggesting feedback inhibition of NOS by NO. 6 EFS induced prominent NO-mediated relaxations in the urethra while minor or no responses were observed in the detrusor and the ureter, respectively. Urethral relaxations to EFS were inhibited by NOS inhibitors with the rank order of potency: L-NOARG = L-NAME>7-NI> L-NMMA. 7In conclusion, we have demonstrated the presence of NO-synthesizing enzymatic activity in the sheep urinary tract which shows similar characteristics to the constitutive NOS isoform found in brain. We suggest that the enzymatic activity measured in the urethral muscle layer may account for the NOmediated urethral relaxation during micturition whereas regulation of detrusor and ureteral motor function by NOS containing nerves is less likely. Keywords: Nitric oxide; nitric oxide synthase; urethra; detrusor; ureter; nitrergic relaxation; urinary tract Introduction It has been suggested that nitric oxide (NO) has important regulatory functions in the urinary tract acting as a nonadrenergic, non-cholinergic (NANC)-relaxant transmitter. Specially relevant is the proposed role of NO in mediating the decrease in outlet resistance which accompanies micturition (Andersson, 1993). A rich supply of nitrergic nerves has been identified by NADPH-diaphorase histochemistry and nitric oxide synthase (NOS) immunohistochemistry in the outflow region (urethra, bladder neck and bladder base or trigone) of several species including rat (McNeill et al., 1992), pig (Persson et al., 1993), sheep (Triguero et al., 1993 and human (Sme...

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“…Multiple isoforms of adenylyl cyclases exist that catalyze the formation of cAMP Fawcett et al, 2000). In general, increases in cAMP seem to have a main role in bladder relaxation, whereas cGMP is important for urethral relaxation (Morita et al, 1992b;Dokita et al, 1994;Persson and Andersson, 1994;Persson et al, 2001). A decrease of cAMP concentration may increase bladder tone.…”

Section: Peripheral Targetsmentioning

confidence: 99%

“…Nitric Oxide. Not only constitutive NO synthase (neuronal NOS, nNOS; endothelial NOS, eNOS) but also inducible NO synthase (iNOS) can be demonstrated in lower urinary tract smooth muscle from animals and humans (Dokita et al, 1994;Ehren et al, 1994a,b;Olsson et al, 1998;Lemack et al, 1999Lemack et al, , 2000Johansson et al, 2002b;Masuda et al, 2002a,b;Felsen et al, 2003). There is so far no evidence that nNOS is produced by detrusor smooth muscle cells, and in unstimulated detrusor cells, iNOS was not detected.…”

Section: Peripheral Targetsmentioning

confidence: 99%