To investigate the activity of nitric oxide (NO) in control of renal hemodynamics during aging, studies were conducted on conscious Sprague-Dawley rats aged 3-5 mo (young, Y) and 18-22 mo (old, O). Blood pressure (BP) and renal vascular resistance (RVR) were higher in O vs. Y in control, and acute systemic NO synthesis inhibition (NOSI) increased BP and RVR, with an enhanced renal vasoconstrictor response in O. Infusion of the NO substrate L-arginine produced similar, selective renal vasodilation in both groups. The endothelium-dependent vasodilator acetylcholine caused similar falls in BP and RVR, whereas sodium nitroprusside produced an exaggerated depressor response in O vs. Y without falls in RVR in either age group. Urinary excretion of the stable NO oxidation products (NOx) decreased with age, suggesting a decline in the overall somatic NO production. In conclusion, basal tonically produced NO has a more pronounced role in maintenance of renal perfusion in aging, whereas L-arginine- and agonist-stimulated renal vasodilation is not impaired with age. NO production from some source may be reduced with aging, as indicated by falls in 24-h NOX excretion, although the similarity in pressor response and enhanced renal vasoconstrictor response to NOSI suggests that the role of NO in control of total peripheral and renal vascular resistance is maintained.
NO2 + NO3 (NOx), the stable oxidation products of NO, and cGMP are widely accepted as indices of in vivo NO production. Whether acute changes in urinary excretion of nitrite + nitrate (UNOXV) can be taken to reflect acute changes in renal and/or systemic NO production is not known. The present studies were conducted in the conscious rat to investigate the effect on acute changes in UNOxV, of maneuvers that (a) enhance NO production and (b) act as diuretics. L-arginine (L-arg) and acetylcholine (Ach) produce equivalent NO dependent falls in renal vascular resistance (RVR), but a much greater increase in UNOX V is seen with L-arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but produces a large rise in UNOX V, and SNP lowers BP but not RVR and results in a reduced UNOX V. None of the diuretics employed should stimulate the NO system or lower RVR; however, the proximally acting agents, acetazolamide and D-arg increased UNOx V, while the loop diuretic furosemide had little effect. H2O diuresis (a distal event) led to a fall in UNOx V. These data suggest that NOx is reabsorbed extensively in the proximal tubule and that inhibition of proximal reabsorption leads to an increase in UNOx V. Also, our results show that the relationship between UNOx V and UcGMP V is unpredictable. Therefore, we conclude that measurements of acute changes in UNOxV and/or UcGMP V should be interpreted cautiously, since they may reflect altered tubular handling of NOx rather than the acute activity of the systemic and/or renal NO systems.
Explants of epididymis, vas deferens, seminal vesicle, and coagulating gland from 10-12-week-old and 7-8-month-old male Swiss Webster mice were maintained in synthetic media without serum or hormones for up to 28 days. Differences were observed in the survival and responses of each gland and the behavior of the principal and basal cells. Epithelial cell migration was pronounced in the vas, moderate in the epididymis, and low in the seminal and coagulating gland. The incidence of basal cell proliferation, hyperplasia, and squamous metaplasia usually was positively related to the frequency of basal cells in the zero-time explants. Few differences were observed between the survival or responses of explants from young and old animals; however, explant culture appears useful for exploring fundamental properties of each accessory sex gland, especially the properties of basal cells.
E. SPRING-MILLS, C. HILL, and M. APELLANIZThe number of nuclei per principal cell was determined in the vas deferens of sexually immature, young sexually mature and old nlale mice. The incidence of binucleation increased with age. In 21-day-old mice approximately 99% of the cells were mononucleated whereas in 7%-12 month old animals 80%-90% of the principal cells were mononucleated and 9%-20% of the principal cells were binucleated. In the oldest animals, the ampulla and testis end of the vas usually had more binuclear cells than the middle segment. The biological significance and the mechanism of this phenomenon are not known; however, binucleation may prove to be a useful indicator ofaging in the vas of this species. In addition, the mouse vas may provide a useful model for studies of binucleation and mitosis.
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