RESUMEN
OBJECTIVES: To determine whether interstitial cystitis is associated with the increased release of substance P from the bladder wall into urine, by measuring urinary excretion rates of substance P and its metabolites in women with interstitial cystitis and in a control group of women with stress incontinence and normal bladder function. PATIENTS AND METHODS: Catheter urine was collected from 13 patients and 10 controls during a water diuresis ( approximately 10 mL/min) before and after instilling the bladder with 100 mL of water. The contribution of the bladder wall to urinary substance P peptides was assessed by measuring the change in substance P peptide levels after 2 min of bladder stasis before and after instillation. RESULTS: Absolute substance P excretion rates were similar in patients with interstitial cystitis and controls; 2 min of bladder stasis reduced the substance P excretion rate (P = 0.03) and increased the excretion rate of substance P metabolites (P = 0.01). CONCLUSIONS: The release of substance P from the bladder wall was not increased in patients with interstitial cystitis.
Asunto(s)
Cistitis Intersticial/orina , Sustancia P/orina , Cromatografía Líquida de Alta Presión/métodos , Femenino , HumanosRESUMEN
The aim of this study was to test the hypothesis that the relative insensitivity of the ovine fetal kidney to arginine vasopressin (AVP) is due to low levels of expression of the gene for aquaporin-2 (AQP2) which encodes the AVP-regulated water channel. We report the cloning of the cDNA for the ovine AQP2 which has a major transcript at 4.2 kilobases (kb) and a minor transcript at 1.5 kb, resembling the human gene transcripts. At 40-60 days' (term = 145-150 days'), mRNA levels are very low, detectable only by reverse transcription-polymerase chain reaction (RT-PCR). By Northern blot analysis AQP2 mRNA is detectable at 75 days'. The ratio of AQP2/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA increases approximately 2.4-fold between 100 and 140 days' when it is about 41% of adult values. Both glucocorticoids and the renin-angiotensin system are involved in maturation of renal function. When fetuses at 75 or 85 days of gestation were exposed to high levels of dexamethasone for 2-3 days, mRNAs for both GAPDH and AQP2 doubled, but the ratio was unchanged. Angiotensin I, infused for 3 days at 115-120 days' gestation, increased the AQP2/GAPDH mRNA ratios by twofold (major transcript) and sixfold (minor transcript), which were highly significant (P<0.001). The increasing sensitivity of the ovine fetal kidney to AVP, from 100-140 days of gestation, is largely due to increasing AQP2 gene expression over this period.
Asunto(s)
Acuaporinas/genética , ADN Complementario/genética , Riñón/fisiología , Angiotensina I/farmacología , Animales , Acuaporina 2 , Acuaporina 6 , Arginina Vasopresina/farmacología , Northern Blotting , Clonación Molecular , Feto , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Humanos , Inmunohistoquímica , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , OvinosRESUMEN
The expression and regulation of the receptors for angiotensin II (both AT1 and AT2) were examined in the ovine fetal adrenal gland by RNase protection assay (RPA), in situ hybridisation histochemistry, immunohistochemistry and Western blotting. Both mRNA and protein for the AT1 receptor were present in the zona glomerulosa and zona fasciculata of the cortex, but not in the medulla, from as early as these zonas were distinguishable (60 days of gestation; term is 145-150 days), and even present in the steroidogenic cells of the unzoned gland at 40 days. The mRNA for the AT2 receptor was present in the same locations (but never in the medulla) from 40-130 days, and declined to extremely low levels after 140 days. The infusion of ang II, 1 microg/h, for 3 days, at mid-gestation (76 +/- 2 days) caused a significant decrease in mRNA for AT1 but no change in AT2 levels. Thus, the biologically active receptor (in terms of aldosterone stimulation) is present in the ovine fetal adrenal from very early in development, and can be down-regulated by mid-gestation.