Presented October 25th - 28th, 2007 at the 2007 Urological Research Society (URS) Meeting - Napa, California

Objective: Nitric oxide (NO), a neurotransmitter responsible for relaxation activity in the lower urinary tract, is synthesized from L-arginine by nitric oxide synthase (NOS) in a reaction prohibited by NG-nitro-L-arginine methyl ester (L-NAME). The aim of the study is to investigate the effects of chronic treatments with L-arginine and L-NAME on the response of the rabbit to partial bladder outlet obstruction (PBOO).

Methods: Thirty-six adult male New Zealand White rabbits (3~5 kg and 15~20 weeks old) were divided into three groups of 12 rabbits each. Each group was then divided into three subgroups composed 4 rabbits each. Subgroups included no-treatment , L-arginine , and L-NAME treatment. Rabbits in groups 1 and 2 were subjected to 2 and 8 weeks of PBOO respectively. The remaining group underwent sham surgery as controls. The bladders were then removed, weighed, and the tissues used for contractile, histological and immunohistological studies.

Results: There was an equal increase in bladder weight among all groups at 2 weeks obstruction. At 8 weeks obstruction there was a significant augmentation in bladder weight in the no-treatment and L-NAME groups but only a moderate increase was seen in the L-arginine group. In general, there was a declining trend in contractile response to all modes of stimulation at 2 weeks of PBOO and a further drop after 8 weeks obstruction. However, at 8 weeks of PBOO, L-arginine group had significantly greater contractile function in response to field stimulation and carbachol compared to no treatment group; L-NAME group had significantly lower contractile function in response to KCL and ATP compared to no treatment group. In morphological study, after obstruction 2 weeks, all groups showed hyperplasia and hypertrophy of smooth muscle cell. However, at obstruction 8 weeks, denudation of mucosa and atrophy of smooth muscle cell were characteristic in both non-treatment and L-NAME groups; intact of mucosa and muscle cell were well demonstrated in L-arginine group. Immunostaining with anti-CD 31 antibodies showed transmural angiogenesis among all groups at obstruction 2 weeks. At obstruction 8 weeks, vascularization generally decreased in serosal and muscular layer at non-treatment and L-NAME groups; transmural angiogenesis was still found at L-arginine group. The mean number of vessels per unit area was significantly increased among all subgroups at obstruction 2 weeks. However, at obstruction 8 weeks, vessels density decreased to control level at no-treatment group and even lowered at L-NAME group; vessel density was still significantly higher than control level in the L-arginine group.

Conclusions: Blockage of NO by L-NAME resulted in a loss of angiogenesis and decreased blood flow during chronic PBOO and resulted in an increased rate of dysfunction during chronic obstruction. Supplement of the diet with L-arginine maintained increased angiogenesis, increased blood flow, and reduced the level of contractile dysfunction following chronic PBOO.

Authors: Lin WY, Mannikarottu A, Chichester P, Juan YS, Neuman P, Whitbeck C, Kogan B, and Levin RM

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