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  • 1
    ISSN: 1434-0879
    Keywords: Key words Diabetic cystopathy ; Rabbit ; Cyclic AMP ; Cyclic GMP ; Prostacyclin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1434-0879
    Keywords: Key words Endothelin-1 ; Rabbit ; Bladder ; Diabetes mellitus ; Smooth muscle cell proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Urinary bladder hypertrophy and hyperplasia are well recognised in diabetic cystopathy. The urinary bladder is known to synthesise endothelin-1 (ET-1), a potent vasoconstrictor peptide with mitogenic properties. Using diabetic New Zealand White (NZW) rabbits, we investigated the potential role of ET receptor subtypes (ETA and ETB) on the proliferation of bladder smooth muscle cells (SMC). Diabetes mellitus was induced in adult male NZW rabbits. After 6 months, control (n=6) and diabetic (n=6) bladders were removed and SMC from the dome and bladder neck were grown using standard explant methodology. At passage two, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or diabetic rabbit serum (DRS) in the presence or absence of ETA-antagonist (BQ123) or ETB-antagonist (BQ788). SMC proliferation was then measured with 5-bromo-2′deoxy-uracil 24 h later and by cell counting (using a haemocytometer) at 48 h. Neither BQ123 nor BQ788 influenced detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of DRS, BQ123 and BQ788 significantly inhibited diabetic detrusor and bladder neck SMC proliferation at 30 and 100 nmol/l (P 〈 0.03 and P 〈 0.01, respectively). Cell counts were also significantly reduced from the diabetic detrusor and bladder neck (P 〈 0.01 and P 〈 0.03 with BQ123 and BQ788, respectively). These results suggest that ET may play a pathophysiological role in the bladder SMC hyperplasia associated with diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; impotence ; prostacyclin ; penis rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In view of the marked increase in blood flow into the penis during erection and the association of diabetes mellitus with impotence, we used the diabetic rat model to investigate the possibility that: (a) the penis may produce prostacyclin; and (b) prostacyclin secretion may be decreased in diabetes. Rats given a high dose of streptozotocin (120 mg/kg body weight) developed acute ketotic diabetes and were killed after 48 h. Animals given a low dose of streptozotocin (65 mg/ kg body weight) developed non-ketonuric diabetes and were killed after 7 or 62 days. Aortic rings and penile tissue discs were incubated in buffer, which was assayed for 6-oxo-pros-taglandin F1α, the stable and spontaneous breakdown product of prostacyclin. Penile tissue from control, ketotic and non-ketonuric (7 days) animals released similar quantities of prostacyclin, whereas that from long-term non-ketonuric animals (62 days) produced significantly less prostacyclin. Production of this prostanoid by the aortic rings paralleled these changes. We conclude that: (a) penile tissue releases prostacyclin in quantities comparable to those of the aorta; (b) long-term diabetes leads to diminished prostacyclin release by penile and aortic tissue: the former may contribute to the pathogenesis of diabetic impotence; and (c) since short-term ketotic diabetes does not inhibit aortic or penile prostacyclin release, duration of diabetes rather than its severity is responsible for diminished prostacyclin release.
    Type of Medium: Electronic Resource
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