Sexual hormones modulate compensatory renal growth and function / Las hormonas sexuales modulan el crecimiento renal compensador (CRC) y la función renal en la uninefrectomía (uNx)

The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG) that follows uninephrectomy (uNx) is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa) were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50%) while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA) was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content) was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

La importancia que pueden tener las hormonas sexuales y sustancias vasoactivas sobre el crecimiento renal compensador (CRC) que sigue a la uninefrectomía es aún materia de debate. Se estudiaron ratas Wistar de ambos sexos, a los 150 días de vida, intactas y gonadectomizadas con y sin uNx, realizada a los 90 días de vida. Se midió volumen urinario diario y excreción de electrolitos y actividad de kalikreína urinaria. Se midió filtrado glomerular y presión arterial media extrayéndose luego los riñones que fueron pesados y preparados para estudios histológicos y determinación de ADN, ARN y proteínas para estimar contenido nuclear y tamaño celular. El CRC fue calculado comparando el peso del riñón al momento de las uNx (90 dias de vida) con aquel obtenido a los 150 días de vida. En las ratas macho uNx se observó el mayor CRC (50%) mientras que, en los otros grupos uNx solo alcanzó un 25%, 15% y 19%. El filtrado glomerular acompañó los cambios morfológicos observándose el menor filtrado en las ratas hembras uNx respecto al resto de los grupos 0.56 ± 0.02, p < 0.05. El tamaño celular (proteína o ARN/ ADN) fue similar para todos los grupos excepto para los orquidectomizados uNx, cuyo contenido citoplasmático fue menor. El contenido nuclear (ADN) fue semejante en todos los grupos. Se observó que el CRC está influenciado positivamente por las hormonas sexuales masculinas y su ausencia modula el tamaño celular. La falta de hormonas sexuales femeninas, en cambio, afecta negativamente el CRC. El sistema kalikreína kinina no parecería estar involucrado en el CRC.

The Effects of Recombinant IGF-I on Function and Nitric Oxide Synthase Activity of Kidney during Compensatory Hypertrophy / 대한비뇨기과학회지

PURPOSE: Among renotropic agents, a growth hormone(GH) independent insulin-like growth factor I(IGF-I) improves renal function without inducing glomerulosclerosis and its potential for treating renal disease is increasing. To elucidate the effect of externally administered IGF-I toward enhancing renal function, the change in renal function and renal nitric oxide synthase(NOS) activity were investigated in the presence of the GH-IGF-I axis. MATERIALS AND METHODS: 100?150g Sprague-Dawley male rats were classified four groups according to experimental methods. The left kidney were removed in the rats of UNx group(uninephrectomy) and UNx+IGF-I group(IGF-I treated after uninephrectomy), and sham operation were done in the other rats of control group and Sham+IGF-I group(IGF-I treated after sham operation). The UNx+IGF-I group and Sham+IGF-I group were treated with 300microgram of recombinant IGF-I(rhIGF-I) daily for 5days after operation. The NOS activity were determined in the contralateral kidney tissues and the glomerular filtration rate(GFR) and effective renal plasma flow(ERPF) were determined in the serum. RESULTS: The GFR, ERPF and NOS activity significantly increased compared to control after uninephrectomy(p<0.05). The GFR, ERPF and NOS activity were significantly different between UNx+IGF-I group and UNx group(p<0.05), but there was no significant difference between Sham+IGF-I group and Sham group after the administration of rhIGF-I. CONCLUSIONS: Externally administered rhIGF-I increases GFR and ERPF via increasing NOS activity. We suggest that it is especially effective in improving the renal function of damaged kidneys.