Neuroscience Let ters, 135 (1992) 1 ~ 1 © 1992ElsevierScientificPublishers Ireland Ltd. All rights reserved0304-3940/92/$05.00 NSL 08282 Impairment of renal urinary excretion in neonatal, but not in adult capsaicin-pretreated rats Stefano Manzini ~, Carla Bacciarelli 2, Marina Perfumi 3 and Maurizio Massi 3 ~ Menarini Ricerche Sud, Department of Pharmacology, Pomezia, Rome (Italy), 21stituto Farmacobiologieo Malesci, Research Laboratories, Florence ( Baly ) and 31stituto di Farmacologia, University of Camerino, Camerino (Italy) (Received6 June 1991;Revisedversionreceived 18 September 1991;Accepted 18 September1991) Key words. Sensorynerve; Sensoryneuropeptide;Kidney;Diuresis; Natriuresis; Kaliuresis; Dual sensory/efferent function The effectof saline and/or water load on diuresis, natriuresis and kaliuresis in control and in neonatal or adult capsaicin-pretreated awake rats has been assessed. Urine was collectedby means of metaboliccages or intra-abdominallyfrom a previouslycatheterizedureter. Neonatal but not adult capsaicin-pretreatedanimals exhibited a remarkable reduction in volur,- of urine output and in electrolytes excretion.This effectwas more evident following saline as compared to water load. Similar results were al~u ontained when urine was directly collectedfrom the ureters, suggesting that pharmacological ablation, at neonatal stage, of a subset of capsaicin-sensitivesensorynerves could impair the excretorykidney function. Holzer-Petsche and Lembeck [5] have demonstrated that neonatal systemic capsaicin pretreatment reduced by about half the urine excretion in the 3 h following a water load of 5 ml/h g b.wt. Although part of this effect might be a consequence of the impairment in the micturi- tion reflex [10] it was proposed that neonatal capsaicin pretreatment might also have produced a delay in urine production by the kidney [5]. Later on capsaicin- sensitive CGRP-containing structures have been demon- strated in the papilla and medulla, but not in the cortex, of rat kidney [4]. Furthermore a remarkable release of CGRP could be evoked by capsaicin in isolated and perfused rat kidney [4]. In order to ascertain the potential role of the kidney in the reduced recovery of urine in capsaicin-pretreated rats, we have evaluated diuresis, na- triuresis and kaliuresis in the 24 h following saline or water load, in control, neonatal or adult capsaicin-pre- treated rats placed in metabolic cages or whose urines were directly collected from their ureters (thus avoiding possible differences due to impairments in bladder func- tion). Three-month-old Wistar Nossan albino rats of both sexes were used. Body weights averaged 300-350 g (males) and 250-280 g (females). Animals had been treated at day 1 or 2 from birth with capsaicin (or vehi- cle) according to a previously described method [11]. Correspondence: S. Manzini, Menarini Ricerche Sud, Department of Pharmacology,P.O. Box 15302,00143 Roma EUR Laurentino, Italy. Half of the neonatal vehicle-pretreated rats were treated with capsaicin (50 rag/kg, s.c.) at the age of 3 months. The diuresis experiments were performed 4 days later. No significant differences in body weight were observed in control and capsaicin-pretreated rats. Efficacy of cap- saicin pretreatment was checked by the loss of the wiping reflex following capsaicin instillation (0.01%) in the eye. Urine collection in metabolic cages: 2 h before the ex- periments rats were placed in metabolic cages allowing a separate collection of urine and feces. Animals were dosed, by intragastric gavage, with water or isotonic sa- line equivalent to 5% of their body weight. During the experiments, animals had no access to food, while water was available ad libitum. Urine was collected before and 1, 2, 3, 4, 8 and 24 h following saline or water administra- tion. Sodium and potassium concentrations in urine samples were determined by flame photometry (Digi- flame compact, G.D.V, Rome, Italy). In this set of ex- periments only male rats were used and no difference in body weight was observed between control and capsai- cin-pretreated rats. Urine collection from intraureteral catheters: 5 h fast- ing animals were lightly anaesthetized with ether, then the abdomen was opened and the right ureter esterior- ized. One end of a polyethylene catheter (i.d. 0.28 ram; o.d. 0.61 mm) was inserted into the ureteral lumen. The other end was connected to a rubber inflatable reservoir (Penrose drain, length 12 cm; Rusch, F.R.G., cat. no. 473600) which was placed in the abdominal cavity. Cath-