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- Persson, Katarina, et al.
(författare)
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Effects of inhibition of the L-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro
- 1992
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Ingår i: British Journal of Pharmacology. - 0007-1188 .- 1476-5381. ; 107, s. 178-184
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Tidskriftsartikel (refereegranskat)abstract
- 1 The present study was performed to investigate how blockade of the L-arginine/nitric oxide (NO)pathway influences the function of the lower urinary tract in vivo, as studied by cystometry in consciousrats and in vitro, in isolated muscle preparations from the rat detrusor and urethra.2 L-N0-nitro arginine methyl ester (L-NAME), 10 and 20 mg kg-, administered intra-arterially,decreased micturition volume and bladder capacity, and increased spontaneous bladder contractions.D-NAME (20mgkg-') had no effect. No changes in the urodynamic parameters were recorded ifL-NAME (20mgkg-') was administered in combination with L-arginine (200mgkg-').3 Cystometries performed after intra-arterial administration of sodium nitroprusside (SNP) (3mgkg-') and 3-morpholino-sydnonimin hydrochloride (SIN-1, 2mgkg-') showed a decrease in bladdercapacity, micturition volume and threshold pressure. SIN-1, but not SNP, induced spontaneous bladdercontractions.4 Isolated precontracted urethral preparations responded to electrical stimulation with a frequencydependenttetrodotoxin-sensitive relaxation. L-NAME (10-4 M), but not D-NAME, reduced the maximalrelaxation to 31 ± 8% (n = 8) of the response prior to drug administration. The inhibition induced byL-NAME was completely reversed by L-arginine (10-3 M). SNP (10-1 10-4 M), SIN-1 (10-6-3 x l0-4M) and NO (10-5-10-3M; present in acidified solution of NaNO2), caused relaxation (93-100%) ofurethral preparations. L-NAME did not affect these relaxations.5 Detrusor strips contracted by carbachol or K' showed contractions in response to electricalstimulation, even when pretreated with a,p-methylene ATP and/or atropine. Small relaxations (14-41%)of detrusor strips were evoked by SNP (10-6-10-4M), SIN-1 (10-5-3 x 10-4M) and NO (10-5-10-3M). Electrically (20 Hz) induced contractions of the detrusor muscle were unaffected by addition ofL-NAME (10-6_10-4 M) or L-arginine (10-3 M).6 The present results suggest that the L-arginine/NO pathway is of functional importance for thebladder outlet region, but that its role in the detrusor is questionable. They also suggest that the site ofaction of L-NAME for inducing bladder hyperactivity in the rat is the outlet region rather than thedetrusor muscle.
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