Nitric oxide synthase in dog urethra: a histochemical and pharmacological analysis

Abstract

1 To examine the presence of nitric oxide synthase (NOS) activity in female dog urethra, pharmacological experiments were performed using electrical field stimulation (EFS), guanethidine, atropine, NG-nitro-L-arginine methyl ester and L-arginine, NOS immunohistochemistry using specific anti-NOS antibody, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining were also performed. 2 EFS caused frequency-dependent contractions in all urethral preparations, but in the presence of guanethidine and atropine, EFS caused significant relaxation in the proximal urethra and was without effect on the distal urethra. 3 In the presence of guanethidine, atropine, and NG-nitro-L-arginine methyl ester, small contractions to EFS were re-established in the proximal urethra, but not in the distal urethra. NG-nitro-D-arginine methyl ester had no such effect. 4 In the presence of guanethidine, atropine, and NG-nitro-L-arginine methyl ester, the addition of Larginine, restored the EFS-elicited relaxant responses previously seen with guanethidine and atropine alone in the proximal urethra (at 30 Hz; 12.89+5.27% to -2.44+4.43%, mean+s.e., P<0.05). DArginine had no such effect. 5 In the distal urethra, the addition of NG-nitro-L-arginine methyl ester and then L-arginine had no effect on responses to EFS in preparations treated with guanethidine and atropine. 6 Sodium nitroprusside caused relaxation in both the proximal and distal urethra. The relaxant responses per cm2 cross sectional area in the proximal and distal urethra were 1.23 + 0.29, and 2.02 + 0.54 g cm-2 cross sectional area (mean + s.e.), respectively: there was no significant difference between them. 7 Both NOS and NADPH diaphorase-positive neurones were present in dog urethra, the densities of both being higher in the proximal urethra than in the distal urethra. 8 These results show that female dog urethra possesses NOS nerves and that endogenous NO may play a role in relaxation in the proximal but not the distal urethra.

Purinergic signalling in the urinary tract in health and disease

“…Amongst compounds which cause relaxation, the putative transmitter was claimed not to be VIP, ATP, 5-HT or adenosine, because blockade of these responses by pharmacological manipulation did not produce a parallel effect on the neurogenic response [282,295,377,720]. The principal NANC inhibitory transmitter is now clearly established, namely, NO [26,214,258,283,414,563,655,674]. However, a small component of purinergic neurotransmission may also be involved [24,561,563].…”

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Pathophysiology of Voiding Dysfunction and Pharmacological Therapy

“…NO is a neurotransmitter capable of producing smooth muscle relaxation, at least in the female rabbit urethra, pig urethra, dog urethra, and human bladder neck (25,30,31).…”

A pharmacological and histochemical study of hamster urethra and the role of urothelium

“…Pharmacological evidence indicates that nitric oxide (NO) is involved in the non-adrenergic, non-cholinergic (NANC) inhibitory response of the urethra, bladder neck and trigone from various species including: man (Klarskov et al, 1983); pig (Klarskov, 1987a;Persson et al, 1993), rabbit (Dokita et al, 1994;Persson & Andersson, 1994), rat , sheep (Garcia-Pascual et al, 1991), cat (Levin et al, 1992) and dog (Hashimoto et al, 1993;Takeda & Lepor, 1995). The, possible involvement of NO in hamster urethra has not yet been investigated.…”