Acquired urinary incontinence in the canine is a distressing and debilitating condition affecting up to 20% of neutered bitches, whilst less than 1% of entire bitches and males suffer from this condition. Although a number of medical and surgical therapies exist for treatment of acquired urinary incontinence, none are able to cure the condition and many animals become refractory to treatment over time. It has long been thought that a decrease in resting tone within the urethra of a bitch following neutering is responsible for the development of acquired urinary incontinence; however, recent studies show that low urethral tone does not always lead to urinary incontinence, suggesting further factors must be involved. Although the exact aetiology and pathophysiology of the condition in the neutered bitch is unknown, it is thought to have many similarities to that of post menopausal urinary incontinence in women. In this condition, urinary incontinence is known to be mediated primarily by changes in the structure and function of the urinary bladder post menopause. The present study looks at the structure and function of the canine urinary bladder in vitro to determine if changes occur post neutering that could lead a bitch to develop acquired urinary incontinence and which may provide novel therapeutic targets for treatment of this disease. Contractility in response to carbachol (muscarinic) and electrical field stimulation was assessed in isolated strips of detrusor muscle from male and female, intact and gonadectomised canines. The potential role of non-adrenergic, non-cholinergic mediated contraction of the detrusor muscle was also examined and this system does not appear to be significantly altered by gonadectomy. Maximal contractile responses were, however, decreased in detrusor strips from neutered compared to entire canines regardless of gender, with detrusor strips from incontinent bitches having some of the weakest responses. Sensitivity to carbachol was also decreased in detrusor strips from neutered compared to entire canines. This suggests a decrease in contractile function of the urinary bladder in neutered canines and is similar to that seen in the bladders of women suffering from urinary incontinence post-menopause due to impaired contractility of the bladder and idiopathic detrusor instability. This suggests that changes in the function of the bladder post neutering may be partly responsible for the development of acquired urinary incontinence in the bitch. Post-menopausal urinary incontinence in women is hypothesised to be a linked to an increase in the collagen to smooth muscle ratio within the wall of the urinary bladder which is thought to impair bladder contractility and lead to the development of detrusor instability. Morphometric analysis of the urinary bladder wall of canines showed that the percentage of collagen within this organ was significantly increased in neutered compared to entire bitches, with incontinent bitches having some of the highest percentage collagen. The percentage of collagen was unchanged in neutered compared to entire males which were similar to entire bitches. These results support the long postulated theory that a decrease in oestrogen following gonadectomy / menopause is involved in the increase of collagen within the bladder. Results describing the pharmacological characterisation of muscarinic receptors (Schild analysis of pKB values) in strips of canine detrusor muscle suggest that the M3 receptor is the primary receptor responsible for bladder contraction in entire canines in vitro but that the M2 receptor predominates in neutered canines. This previously unreported finding could be significant in providing a novel therapeutic target to treat this debilitating disease. Studies that looked at mRNA expression for the muscarinic as well as the LH and GnRH receptors in canine bladder wall showed that there was an increase in expression of all receptors in tissue from neutered compared to entire canines and that tissue from females had higher expression levels than that from their male counterparts. It is known that gonadotrophin levels in the blood increase post neutering, and that decreasing these levels can provide continence in a number of animals. It is therefore possible, that an up-regulation of mRNA expression for these receptors is involved in the changes at the level of the detrusor that could lead to development of acquired urinary incontinence. It is also acknowledged that the muscarinic pathway is the primary pathway responsible for bladder contraction and emptying, therefore, a change in the expression of muscarinic receptors has the potential to alter bladder contractility as demonstrated previously. In conclusion these studies have shown that the structure and function of the urinary bladder of a neutered canine is altered compared to that of an entire canine, and that these changes have the potential to be involved in the development of acquired urinary incontinence in the bitch. Many of these changes mimic those seen in the bladders of post menopausal women suffering from urinary incontinence, thus suggesting that there may be commonality of disease process between the two species which may allow the use of the canine as a model of human urinary incontinence. This data, the first to include male animals in the study of bladder function and structure, suggest that the loss of oestrogen in the female and the concurrent increase in percentage collagen within the urinary bladder are not significant factors in the development of decreased detrusor contractility per se. On the contrary these results suggest that the muscarinic receptor effector pathway may play a crucial role in the development of altered bladder contractility and acquired urinary incontinence, and may provide a therapeutic target for effective treatment of this disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:513346 |
| Date | January 2009 |
| Creators | Coit, Victoria Ann |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/855/ |
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