A Histochemical and Immunohistochemical Study of the Autonomic Innervation of the Lower Urinary Tract of the Female Pig. Is The Pig a Good Model for the Human Bladder and Urethra?

Abstract

The detrusor muscle, bladder neck, proximal, middle and distal regions of the urethra of the female pig were studied by histochemical and immunohistochemical methods to localize catecholamine-containing, acetylcholinesterase-positive and peptide-containing nerves. The peptides examined included: vasoactive intestinal polypeptide, substance P, somatostatin, [Met]enkephalin, bombesin and gastrin. The greatest density of nerves was found in the smooth muscle of the distal urethra, followed by the bladder neck, middle urethra, and proximal urethra, with the least in the detrusor muscle. The greatest number of nerve fibres stained for acetylcholinesterase, followed by vasoactive intestinal polypeptide- and catecholamine-containing fibres. Substance P-immunoreactive nerve fibres were confined to the bladder neck and distal urethral regions. [Met]enkephalin-and gastrin-immunoreactive nerves were most dense in the distal urethra but absent in detrusor muscle, while somatostatin-immunoreactive nerve fibres were sparsely distributed throughout the lower urinary tract. No nerve fibres showing immunoreactivity to bombesin were found. Catecholamine-containing, acetylcholinesterase-positive, vasoactive intestinal polypeptide-, substance P-, [Met]enkephalin- and gastrin-immunoreactive nerves were also found on the adventitial-medial border of blood vessels in the pig urinary tract. In the intrinsic external urethral sphincter, located in the distal urethra, vasoactive intestinal polypeptide- and gastrin-immunoreactive nerve fibres were found bordering a small number of individual striated muscle fibres, while catecholamine-containing nerves were found predominantly in the connective tissue surrounding the striated muscle fibres. Dense populations of acetylcholinesterase-positive nerve fibres were found associated with the striated muscle fibres, with end plates on some of them. Intramural ganglia, composed of two to 30 neurones, were found in the bladder neck and middle and distal regions of the urethra. In the smooth muscle, and in the vicinity of the striated muscle regions of the intrinsic external urethral sphincter, there were small ganglia, containing two to three neurones, which were vasoactive intestinal polypeptide-, [Met]enkephalin- and somatostatin-immunoreactive. The results are compared to the autonomic innervation of the human bladder and urethra as previously described and it is concluded that the lower urinary tract of the pig is a good model for some features of the lower urinary tract of man, but a poor model for others.

Immunohistochemical characteristics and distribution of neurons in the intramural ganglia supplying the urinary bladder in the male pig

“…These mentioned functions require a complex neural control system that coordinates the activities of a variety of effector structures including the smooth muscle of the urinary bladder and the smooth and striated muscle of the urethral sphincters Arner 2004, Fowler et al 2008). It has been well recognized so far that the innervation of the urinary bladder is supplied by three sets of peripheral nerves: sacral parasympathetic (pelvic nerves consisting of mainly preganglionic fibres supplying the intramural ganglia as well as of postganglionic fibres (Crowe and Burnstock 1989, Gabella 1990, Birder et al 2009), thoracolumbar sympathetic (hypogastric nerves -their fibres are mainly postganglionic and a few preganglionic supply so called short adrenergic neurons' found within ganglia located very close to pelvic organs (Downie 1981, Feher andVajda 1981) and sacral sensory (pudendal nerves (De Groat and Booth 1993). These pathways are a structural basis for constitution of reflexes, which either keep the bladder in a relaxed state, enabling urine storage at low intravesical pressure, or which initiate bladder emptying by relaxing the outflow region and contracting detrusor muscle.…”

Contractile properties of the proximal urethra and bladder in female pig: Morphology and function

“…Studies have been published which focussed on the mechanical properties of di¡erent muscle layers in bladder and urethra measured in di¡erent animal species, with the aim to relate these properties to the function of both organs. Amongst others, the pig bladder-urethra complex has been used for many years to study (dys)function of the human lower urinary tract [Sibley, 1984;Crowe and Burnstock, 1989]. Recently, it was shown on the basis of magnetic resonance (MR) images compared with histological preparations that pig [Teu£ et al, 1997] and human [Dixon and Gosling, 1983;Narumi et al, 1993;Teu£ et al, 1997] bladder wall are of similar composition and that both consist of urothelium, lamina propria and an inner and an outer tunica muscularis.…”

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

“…Several histological studies (Gu et al, 1984;Crowne & Burnstock, 1989) (Andersson et al, 1983). However, our results showing that EFS with guanethidine and atropine did not elicit relaxation or contraction indicate the lack of any NANC relaxant innervation.…”