Chronic vascular constrictions and measurements of renal function in conscious rats

Although a tremendous amount of physiologic information has been gained from experiments on anesthetized animals, there is often the question to what extent anesthesia itself, as well as the losses and replacement of fluid that accompany surgical preparations, might have influenced the function being studied. This possible pitfall may apply especially to studies on the kidney because the renal circulation is so exquisitely sensitive to anesthetic agents and changes in fluid balance. Chronic preparations in dogs have been [1] and continue to be used [2] successfully. But the far lesser expense of rats, as well as their common use in physiologic experiments, points up the desirability of a successful chronic preparation in this species. Renal clearances have been performed previously on unanesthetized rats [3, 4], but the methods have not been generally adopted.We here describe a method that can measure renal clearances and extraction of PAH accurately and repeatedly in the same conscious rat over a period of weeks. For our own purposes [5] we also needed a method for constricting blood vessels. The design and construction of a suitable cuff for this purpose, likewise usable in unanesthetized rats, also form part of this report

GFR and the concentration of urine in the absence of vasopressin. Berliner-Davidson re-explored

Robert W. Berliner made many important contributions to our understanding of the urinary concentrating mechanism. Among these, one must number his demonstration that urine can be rendered hyperosmotic to plasma even when vasopressin is absent, as well as his definition of the role of the glomerular filtration rate (GFR) in the concentrating process [1, 2]—points that had also been suggested by several other investigators [reviewed in 3, 4]. In postulating how urine might be concentrated without vasopressin purely by changes occurring within the kidney [1], Dr. Berliner expressed the essence of a message, which we still tend to overlook today, namely, that “…although it is commonly stated that the function of ADH is to cause the excretion of a hypertonic urine, its more important function might be better defined as preventing the excretion of a dilute urine.”The availability of the Brattleboro rat, which has an inherited deficiency for synthesizing vasopressin [5], made it possible to further explore the mechanisms by which urine can be concentrated in the apparent absence of the hormone. We here review these experiments, paying special attention to the role of GFR in the process

Renal Dysfunction: Mechanisms Involved In Fluid And Solute Imbalance

https://works.swarthmore.edu/alum-books/3543/thumbnail.jp

Anatomy of a phenomenon

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Renal Function: Mechanisms Preserving Fluid And Solute Balance In Health

https://works.swarthmore.edu/alum-books/3544/thumbnail.jp

Cellular Action of Antidiuretic Hormone in Mice with Inherited Vasopressin-Resistant Urinary Concentrating Defects

Previous work has suggested that resistance to vasopressin in two strains of mice with nephrogenic deficiency of urinary concentration may entail a defect in the action of vasopressin at the cellular level. Several components involved in this action were therefore examined in vitro in renal medullary tissues from control mice (genotype VII +/+) and two genotypes with mild diabetes insipidus (DI +/+ nonsevere) and marked (DI +/+ severe) vasopressin-resistant concentrating defects. No significant differences were found in the affinity of adenylate cyclase for [8-arginine]-vasopressin (AVP), tested over a range of hormone concentration from 10(-10) to 10(-5) M. However, maximal stimulation of adenylate cyclase by saturating concentrations of AVP (intrinsic activity) was markedly decreased from control values in DI +/+ severe mice, and decreased to a lesser extent in DI +/+ nonsevere animals. A significant correlation was found between the activity of adenylate cyclase maximally stimulated by AVP in a given genotype, and the urine osmolality in the same animals. There were no significant differences in maximal stimulation of renal medullary adenylate cyclase in control experiments: not when stimulated nonspecifically by sodium fluoride, nor when stimulated by AVP in tissues from rats with induced water diuresis as compared to antidiuretic rats. Nor were there significant differences between VII +/+ and DI +/+ severe mice in the activity of renal cortical adenylate cyclase, either basal or when stimulated by parathyroid hormone. Furthermore, the abnormal genotypes did not differ significantly from control mice in the renal medullary activities of cyclic AMP phosphodiesterase or cyclic AMP-dependent protein kinase, nor in the content of microtubular subunits (assessed as colchicinebinding protein). The results are compatible with the view that impaired stimulation of renal medullary adenylate cyclase by vasopressin might be the sole or contributing cause of the vasopressin-resistant concentrating defect in the diseased mice; however, a causal relationship has not yet been proved