Alterations in the formation of cyclic nucleotides and prostaglandins in the lower urinary tract of the diabetic rabbit

Abstract

Dysfunction of the urinary bladder is a recognised complication of diabetes mellitus (DM) which has been attributed, in part, to a direct effect on bladder smooth muscle tissue. The objective of this study was to investigate the effect of alloxan-induced DM on endogenous modulators of smooth muscle tone such as cyclic AMP (cAMP), cyclic GMP (cGMP) and prostaglandins. Male New Zealand white rabbits were rendered diabetic (hyperosmolar, non-ketotic) with an i.v. injection of alloxan. After 6 months, the urinary bladders and urethrae were excised, cut into segments, incubated with stimulators and the formation of prostaglandins (PG), cAMP and cGMP measured using radioimmunoassays. PGE₂ and PGI₂ formation was impaired in response to arachidonic acid stimulation, whereas it was increased in response to acetylcholine in DM detrusor, bladder neck and urethra compared to controls. Cyclic AMP and cGMP formation in response to forskolin and sodium nitroprusside, respectively, was significantly reduced in the DM tissues of the lower urinary tract compared to the control. Alterations in the formation of prostaglandins, cAMP and cGMP by the smooth muscle of DM lower urinary tract suggests that these biochemical mediators may have a pathophysiological role in the urinary bladder dysfunction associated with DM.