Rat bladder in the early stages of streptozotocin-induced diabetes: adrenergic and cholinergic innervation

Abstract

Summary. The adrenergic and cholinergic innervation of the bladder was studied in streptozotocin-diabetic rats. The presence of hypertrophy and distension in the 'diabetic' bladders necessitates care in assessing changes occurring in the nerves, factors which are also relevant to clinical histochemical studies. Biochemical assays of cholinergic enzymes revealed decreased activities per g wet weight tissue. However, the total activities of choline acetyltransferase and acetylcholinesterase per whole bladder were significantly increased after 2 weeks of diabetes with greater changes by 8 weeks. Total dopamine levels per bladder were significantly higher than in control rats in the 2-week but not the 8-week group of animals; this may indicate an initial increase in adrenergic nerve activity. There was no impairment in the ability of the detrusor muscle to respond to noradrenaline, acetylcholine or to cholinergic nerve stimulation. Shortly after induction of diabetes streptozotocin-treated rats display polyuria. It is proposed that the activity of the bladder is therefore stimulated to allow greater volumes of urine to be passed. The results are discussed in relation to human diabetes mellitus where clinical studies have implicated a neuropathic origin to bladder dysfunction.Key words: Bladder, diabetic rats, adrenergic nerves, cholinergic nerves, polyuria, neuropathy.Clinical studies on bladder function in patients suffering from diabetes mellitus have reported that an early indication of dysfunction is increased bladder capacity and size, the incidence of such abnormalities has been reported as being as high as 87% in a group of juvenileonset diabetic patients [21]. Later stages are associated with atony of the bladder and urinary retention [16,21,29], and recent literature reveals that the clinical treatment of these symptoms is still under discussion [19,32, 39]. Several studies have correlated the presence of abnormalities in the bladder with signs of peripheral neuropathy [4,5,17]. In addition, clinical investigations of bladder innervation and function have led to the conclusion that bladder dysfunction is a manifestation of autonomic neuropathy in diabetes mellitus [3,7,15,20]. In particular, a defect in the sensory nerves of the bladder has been implicated as the cause of bladder distension in diabetic patients, whilst incomplete bladder emptying occurs as a result of impaired detrusor activity [5,6,16,36]. Histochemical studies on diabetic patients [20] and the diabetic Chinese hamster [10] have revealed reduced staining for acetylcholinesterase in the 'diabetic' bladder, and consequently it has been suggested that an alteration in the cholinergic innervation of the bladder may be one factor involved in bladder dysfunction.In the present investigation, bladder dysfunction was studied in the early stages of streptozotocininduced diabetes in rats, an animal model of juvenileonset diabetes. Distension and hypertrophy of the bladder occurred rapidly after the onset of diabetes, and the adrenergic and choliner...

Elevated levels of vasoactive intestinal peptide in the eye and urinary bladder of diabetic and prediabetic Chinese hamsters

“…In agreement with a previous study [9], the increase of VIP concentration in the expanded bladder of the diabetic Chinese hamster appears to be meaningful since it can be demonstrated on a pmol/organ basis. This contention is reinforced by the finding of increased acetylcholinesterase activity in the expanded bladder of streptozotocin-diabetic rats [9]. Furthermore, the elevation of VIP in the bladder of the diabetic Chinese hamster may be more meaningful since it has been shown that in-A.…”

“…Therefore, it is logical to hypothesize that an elevation in VIP may be one of the early complications related to bladder dysfunction in the diabetic Chinese hamster. Support for this hypothesis is derived from a previous investigation in which an increase in cholinergic nerve activity was observed in the distended bladders of short-term streptozotocin-diabetic rats [9]. It was also suggested that elevated cholinergic nerve activity in streptozotocin-diabetic rats is probably a compensatory response to allow the hypertrophied detrusor muscle to respond to increased volume and frequency of urine [10].…”

“…Although the specific type of lesion varies among animals and man, the vasculature of the eye is always adversely affected [5]. Several investigations have demonstrated that distension [6][7][8][9] and hypertrophy [10] concomitant with urine retention are characteristic of the urinary bladder of diabetic man and animals. Urinary bladder dysfunction is believed to be a product of diabetic autonomic neuropathy [11,12] which promotes impairment of detrusor muscle function [8,13].…”

“…Urinary bladder dysfunction is believed to be a product of diabetic autonomic neuropathy [11,12] which promotes impairment of detrusor muscle function [8,13]. Although it has recently been disputed [9], a reduction in cholinergic innervation [7,14] has been proposed as a possible mechanism which elicits bladder dysfunction. Despite intensive research, the primary aetiological agent(s) underlying the derangements in the eye and urinary bladder of diabetic man and animals remain under investigation.…”

Effects of ONO-2235, an Aldose Reductase Inhibitor, on Muscarinic Receptors and Contractile Response of the Urinary Bladder in Rats with Streptozotocin-Induced Diabetes

“…The motor activity of the smooth muscle, especially that of the bladder dome, is mainly regulated by the parasympathetic nervous system (8,9). Histochemical and functional studies have shown a DM-induced alteration in cholinergic innervation as well as an altered sensitivity to cholinergic agonists (10)(11)(12)(13). Recent in vitro studies showed that the contractile response to muscarinic agonists was increased about 50% in the bladder dome of rats with streptozotocin (STZ) induced DM (14,15), and this was accompanied by sig nificant increases in the densities of muscarinic receptors in the bladder dome of rats (14,16,17).…”