EFFECTS OF INHIBITION OF THE L-ARGININE NITRIC-OXIDE PATHWAY IN THE RAT LOWER URINARY-TRACT INVIVO AND INVITRO
EFFECTS OF INHIBITION OF THE L-ARGININE NITRIC-OXIDE PATHWAY IN THE RAT LOWER URINARY-TRACT INVIVO AND INVITRO
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DOI：
10.1111/j.1476-5381.1992.tb14483.x
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发表时间：
1992-09-01
影响因子：
7.3
通讯作者：
ANDERSSON, KE
中科院分区：
文献类型：
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作者：
PERSSON, K;IGAWA, Y;ANDERSSON, KE
1本研究旨在研究L-精氨酸/一氧化氮（NO）通路的阻断如何影响体内下尿路的功能，如通过清醒大鼠膀胱测压法和体外大鼠逼尿肌和尿道分离肌肉制备物中的膀胱测压法所研究。2 L-N（G）-硝基精氨酸甲酯（L-NAME），10和20 mg kg-1，动脉内给药，排尿量和膀胱容量减少，自发性膀胱收缩增加。D-NAME（20 mg kg ~（-1））无明显作用。如果L-NAME（20 mg kg-1）与L-精氨酸（200 mg kg-1）联合给药，则未记录到尿动力学参数的变化。3动脉内给药硝普钠（SNP）（3 mg kg-1）和3-吗啉代-盐酸西德诺明（SIN-1，2 mg kg-1）后进行的膀胱测压显示膀胱容量、排尿量和阈值压力降低。SIN-1，而不是SNP，诱导自发性膀胱收缩。4孤立的预收缩尿道准备响应电刺激与频率依赖性河豚毒素敏感性松弛。L-NAME（10（-4）M），而不是D-NAME，将最大舒张降低至给药前反应的31 ± 8%（n = 8）。L-精氨酸（10（-3）M）可完全逆转L-NAME的抑制作用。SNP （10（-8）-10（-4）M）、SIN-1（10（-6）-3 x 10（-4）M）和NO（10（-5）-10（-3）M;存在于NaNO 2的酸化溶液中）引起尿道准备物松弛（93-100%）。L-NAME并不影响这些松弛作用。5由氨甲酰胆碱或K+收缩的逼尿肌条在电刺激下显示收缩，即使用α、β-亚甲基ATP和/或阿托品预处理也是如此。SNP（10（-6）-10（-4）M）、SIN-1（10（-5）-3 x 10（-4）M）和NO（10（-5）-10（-3）M）诱发逼尿肌条的小松弛（14-41%）。电（20 Hz）诱导的逼尿肌收缩不受L-NAME（10（-6）-10（-4）M）或L-精氨酸（10（-3）M）的影响。6目前的结果表明，L-精氨酸/NO通路对膀胱出口区域具有重要的功能，但其在逼尿肌中的作用值得怀疑。他们还表明，L-NAME诱导大鼠膀胱过度活动的作用部位是出口区域而不是逼尿肌。
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 conscious rats and in vitro, in isolated muscle preparations from the rat detrusor and urethra.2 L-N(G)-nitro arginine methyl ester (L-NAME), 10 and 20 mg kg-1, administered intra-arterially, decreased micturition volume and bladder capacity, and increased spontaneous bladder contractions. D-NAME (20 mg kg-1) had no effect. No changes in the urodynamic parameters were recorded if L-NAME (20 mg kg-1) was administered in combination with L-arginine (200 mg kg-1).3 Cystometries performed after intra-arterial administration of sodium nitroprusside (SNP) (3 mg kg-1) and 3-morpholino-sydnonimin hydrochloride (SIN-1, 2 mg kg-1) showed a decrease in bladder capacity, micturition volume and threshold pressure. SIN-1, but not SNP, induced spontaneous bladder contractions.4 Isolated precontracted urethral preparations responded to electrical stimulation with a frequency-dependent tetrodotoxin-sensitive relaxation. L-NAME (10(-4) M), but not D-NAME, reduced the maximal relaxation to 31 +/- 8% (n = 8) of the response prior to drug administration. The inhibition induced by L-NAME was completely reversed by L-arginine (10(-3) M). SNP (10(-8) - 10(-4) M), SIN-1 (10(-6) - 3 x 10(-4) M) and NO (10(-5) - 10(-3) M; present in acidified solution of NaNO2), caused relaxation (93-100%) of urethral preparations. L-NAME did not affect these relaxations.5 Detrusor strips contracted by carbachol or K+ showed contractions in response to electrical stimulation, even when pretreated with alpha,beta-methylene ATP and/or atropine. Small relaxations (14-41%) of detrusor strips were evoked by SNP (10(-6) - 10(-4) M), SIN-1 (10(-5) - 3 x 10(-4) m) and NO (10(-5) - 10(-3) m). Electrically (20 Hz) induced contractions of the detrusor muscle were unaffected by addition of L-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 the bladder outlet region, but that its role in the detrusor is questionable. They also suggest that the site of action Of L-NAME for inducing bladder hyperactivity in the rat is the outlet region rather than the detrusor muscle.