Harry O. Senekjian

Alpha and Beta Adrenergic Agonists Stimulate Water Absorption in the Rat Proximal Tubule

SummarySimultaneous capillary and luminal microperfusion studies were performed in the rat proximal tubule to determine the effects of the beta agonist isoproterenol and the alpha agonist phenylephrine on water absorption. Capillary and luminal perfusion solutions were composed such that organic solutes were not present, no bicarbonate was present in the lumen, and no chloride gradient was imposed. Under such conditions, water absorption (Jv) averaged 0.36±0.11 nl·min−1·mm−1. The addition of isoproterenol to the capillary solution in concentrations of 10−6 and 10−4m resulted in significantly higherJvs of 0.68±0.10 and 0.71±0.11 nl·min−1·mm−1, respectively. The enhancing effect of isoproterenol was inhibited by the beta blocker propranolol (10−4m), but not by the alpha blocker phentolamine (10−7m). The addition of phenylephrine (10−6m) to the capillary perfusion solution also resulted in a significantly higherJv of 0.84±0.14 nl·min−1·mm−1, an effect inhibited by phentolamine (10−7m), but not by propranolol (10−4m). Neither phentolamine nor propranolol alone in the concentrations indicated had an effect on water absorption. These experiments indicate that both alpha and beta agonists stimulate water absorption in the superficial proximal tubule of the rat. This effect appears to be relatively specific for each class of agonist, as demonstrated by the effects of the specific antagonists.

Efficacy of intravenous vancomycin in the treatment of gram-positive peritonitis in long-term peritoneal dialysis

Peritonitis is the major complication of long-term peritoneal dialysis. Gram-positive bacteria are responsible for two thirds of the total number of peritonitis episodes. Conventional therapy consists of daily administration of antibiotics, either parenterally or intraperitoneally. Vancomycin, an antibiotic with a prolonged half-life in renal failure, has a wide spectrum of activity against gram-positive bacteria and diffuses readily across the peritoneal membrane. In the present study, 82 percent of gram-positive peritonitis episodes were cured following the intravenous administration of vancomycin at weekly intervals. This cure rate compares favorably with that obtained following conventional therapy of peritonitis. It is concluded that intravenous vancomycin is an effective treatment for gram-positive peritonitis in patients undergoing long-term peritoneal dialysis. This form of therapy is convenient, reduces hospitalization, minimizes cost, and avoids possible contamination of the peritoneal dialysate used during the intraperitoneal administration of antibiotics.

Stopped-flow microperfusion studies of urate absorption from the rat proximal tubule.

Abstract The absorptive flux of [2-14C]urate in the rat proximal tubule was examined using stopped-flow and continuous-flow microperfusion techniques. In the stopped-flow studies, the luminal perfusion was a steady-state equilibrium solution and the luminal contact time was 60 sec. The ratio of disintegrations per minute (dpm) of urate in the reaspirated sample to the initial solution (C/I) was 0.42 ± 0.02 in control experiments. The addition of either phloridzin or ρ-chloromercuribenzoate to the perfusion solution resulted in significantly higher C/I ratios of 0.52 ± 0.03 (P < 0.05) and 0.61 ± 0.006 (P < 0.01), respectively. Substitution of choline for sodium in the perfusion solution or the addition of probenecid did not significantly change the C/I ratio. In continuous-flow microperfusion studies, the fractional absorption of urate from an isotonic saline solution averaged 10.2 ± 0.8%/mm tubule and was significantly inhibited by the addition of probenecid to the perfusion solution. Urate absorption from a steady-state perfusion solution averaged 4.7 ± 1.0%/mm tubule (P < 0.01 compared to the saline solution) and was not affected by the addition of probenecid. These studies indicate that the presence of either phloridzin or ρ-chloromercuribenzoate in the solution bathing the luminal side of the rat proximal tubule cells inhibits urate absorption. Neither the substitution of choline for sodium in the perfusion solution nor the addition of probenecid to the perfusion solution had any significant effect. The failure to demonstrate an effect of probenecid in the stopped-flow studies may have been due to the requirement to use a non-water absorbing solution. When water absorption is permitted to occur, the addition of probenecid to the perfusion solution inhibited urate absorption.

Effects of MK-196 on urate and electrolyte excretion in the rat.

Clearance and micropuncture techniques were used to evaluate the effects of MK-196 on uric acid and electrolyte excretion by the rat kidney. The urinary excretion of sodium, uric acid, calcium and magnesium increased significantly following MK-196 administration. The major site of action with respect to sodium reabsorption was in the ascending limb of Henles loop as revealed by depression of both free-water clearance and reabsorption. By contrast, microinjection studies with [2-14C]-urate revealed the major site of altered urate absorption to be in the proximal convoluted tubule, a site where sodium and water reabsorption was unchanged.

Water Absorption in the Proximal Tubule: Effect of Bicarbonate, Chloride Gradient, and Organic Solutes

Abstract Simultaneous in vivo capillary and luminal microperfusion studies were performed in the superficial proximal convoluted tubule of the rat to determine the effect of intraluminal bicarbonate, the imposition of a transepithelial chloride gradient, and the addition of organic solutes to the luminal perfusion solution on the rates of water absorption (J v). The capillary perfusion solution contained NaCl, NaHCO3, and KCl. Perfusion of both capillary and lumen with the same solution resulted in a J v of 3.01 ± 0.24 nl/min/mm. Imposition of a transepithelial chloride gradient (equimolar substitution of NaCl for NaHCO3 in the luminal solution) resulted in a J v of 3.18 #pL 0.21 nl/min/mm (P = NS). Addition of cyanide to both solutions in the presence of a chloride gradient resulted in a significantly lower J v of 2.21 ± 0.19 nl/min/mm. Luminal substitution of Na cyclamate for NaHCO3 resulted in a solution containing no bicarbonate and no chloride gradient. J v averaged 0.34 ± 0.08 nl/min/mm. Addition of cyanide to the solution totally inhibited J v. The addition of D-glucose, L-alanine, or both, to luminal solutions containing bicarbonate or in the presence of a chloride gradient did not significantly affect J v. Addition of both organic solutes to the NaCl-Na cyclamate luminal solution resulted in a significantly higher J v of 0.77 ± 0.14 nl/min/mm. These studies indicate that J v in the rat superficial proximal tubule is influenced by active sodium transport, by the presence of bicarbonate in the lumen, and/or by the imposition of a transepithelial chloride gradient. The organic solutes D-glucose and L-alanine also influence water absorption, but this effect could only be demonstrated under some experimental conditions.