Effect of furosemide on renal handling of glucose in the rat.

Clearance and intratubular microinjection studies were performed in rats during extracellular volume expansion before and after furosemide administration to evaluate renal tubular transport of glucose. Three groups of animals were studied: group I, intact rats; group II, acutely thyroparathyroidectomized rats; and group III, thyroparathyroidectomized rats receiving parathyroid extract after a control period. In all groups furosemide caused a significant increase in the urinary flow rate and sodium excretion. There was no significant change in filtered glucose and glucose excretion. After early distal tubular injections of [14C]glucose, recovery was complete both before and after furosemide infusion. Furosemide had no effect on [14C]glucose recovery after the late proximal injection. These results indicate that furosemide has no effect on the renal handling of glucose in normoglycemic rats. There is no evidence for glucose reabsorption in the nephronal segments distal to the early distal tubular segment in this experimental state. Our data suggest, but do not prove, that no glucose is transported by the rat nephron beyond the pars recta during normoglycemia.

Effects of extracellular volume expansion on the tubular reabsorption of glucose. A microinjection study.

Clearance and intratubular injections of (14C) glucose were performed in glucose loaded rats, during control (C) and extracellular fluid volume expansion (VE) to 10% of body weight. VE resulted in a significant decrease in hematocrit from 47.50 +/- 1.06 to 38.80 +/- 1.14% and plasma protein from 6.23 +/- 0.25 to 4.13 +/- 0.21 gm/100 ml. Glomerular filtration rate (GFR) increased by 51% from 1.06 +/- 0.07 to 1.60 +/- 0.35 ml/min. Fractional excretion of sodium increased significantly from 0.42 +/- 0.07 to 12.58 +/- 1.25%. Maximal glucose reabsorption (TmG) was unchanged from 3.47 +/- 0.42 to 3.29 +/- 0.41 mg/min. However, TmG/GFR decreased significantly from 3.14 +/- 0.22 to 1.94 +/- 0.21 mg/ml GFR. As compared to C, VE resulted in a significant increase in (14C) glucose recovery after injection into the early and late proximal tubules, from 63 +/- 3 to 81 +/- 2% to 88 +/- 1% respectively. After distal tubular injections (14C) glucose recovery was complete in both C and VE; early distal injection 97 +/- 1 vs 98 +/- 1%, late distal injection 98 +/- 1 vs 99 +/- 1%. These results indicate an inhibitory effect of VE on fractional glucose reabsorption in the superficial nephron. There is no evidence for glucose reabsorption in the superficial distal nephron during C and VE.

Distribution of renal blood flow in dogs with congestive heart failure.

Studies were performed to determine whether the intrarenal distribution of cortical blood flow is altered in congestive heart failure. Utilizing the radioactive microsphere method, we studied eight dogs that developed congestive heart failure secondary to the construction of an aortocaval fistula. They had marked reduction in total renal blood flow not accompanied by intracortical redistribution of blood flow. All dogs had developed edema and/or ascites, and gained a mean of 3.4 kg; glomerular filtration rate, hematocrit, and urinary sodium excretion fell significantly. Renal vascular resistance increased; mean blood pressure and filtration fraction were unchanged. Furosemide was administered to a second group of nine fistula dogs. The drug produced a marked natriuresis associated with a decrease in outer cortical blood flow (zone 1) and an increase in midcortical zones 2 and 3; no change was observed in zone 4. We conclude: 1) chronic salt retention occurs in high-output heart failure in the absence of redistribution of renal cortical blood flow, and 2) the effect of furosemide on intrarenal hemodynamics of dogs with heart failure is similar to that seen in normal animals.

Effect of infusion of pharmacologic amounts of vasopressin on renal electrolyte excretion.

Aqueous vasopressin was infused to bicarbonate- and glucose-loaded dogs and to nonloaded antidiuretic dogs in doses of 50 mU/kg per min or 50 mU/kg per h. Both doses caused a marked increase in sodium, chloride, and water excretion. The larger dose raised the fractional excretion (sodium clearance (C-Na)/glomerular filtration rate (GFR) times 100) of these ions from 2% or less to in excess of 20%. Blocking the pressor effects of these doses of vasopressin with sodium nitroprusside did not alter the marked natriuretic and chloriuretic effect. The maximal rate of bicarbonate and glucose reabsorption was not depressed by vasopressin infusion; fractional phosphate excretion, however, was markedly increased. Inhibiting distal hydrogen ion secretion by inducing selective aldosterone deficiency failed to uncover a vasopressin-induced inhibition of proximal bicarbonate reabsorption that might have been masked by increased distal bicarbonate reabsorption. There was no significant change in GFR, renal plasma flow, or filtration fraction. The distribution of cortical renal blood flow (measured by the radioactive microsphere technique) shifted toward the inner cortex after vasopressin administration. Vasopressin, in pharmacologic doses, is a potent diuretic that most likely exerts this effect by directly inhibiting sodium reabsorption at a point in the nephron distal to the proximal tubule.

Physiology of antidiuretic hormone and the interrelationship between the hormone and the kidney.

This paper reviews the physiology of antidiuretic hormone, including the factors involving the formation, storage and release of the hormone, the metabolism of vasopressin and its physiologic and pharmacologic effects on water and electrolyte transport. The consequences of both deficiency and excess of the hormone are also discussed.

A comparison of the segmental analysis of sodium reabsorption during Ringer's and hyperoncotic albumin infusion in the rat.

Studies were designed to compare the segmental analysis of sodium reabsorption along the nephron during volume expansion with either 10% body weight Ringer's or 0.6% body weight hyperoncotic albumin. Total kidney and nephron glomerular filtration rate increased similarly with both, but urinary sodium excretion (12.7 vs. 4.0 mueq/min, P < 0.001) and fractional sodium excretion (5.0 vs. 1.6%, P < 0.001) increased to a greater extent with Ringer's. Fractional reabsorption of sodium in the proximal tubule was diminished in both groups but to a significantly greater extent during Ringer's (P < 0.005). Absolute reabsorption was inhibited only in the Ringer's group. Delivery of filtrate out of the proximal tubule was greater in the Ringer's studies, 45 vs. 37 nl/min (P < 0.001). However, both fractional and absolute sodium delivery to the early and late distal tubule were not significantly different in the two groups. Fractional reabsorption in the collecting duct decreased from 96% in hydropenia to 31% during Ringer's but fell only slightly to 80% in the albumin studies. Absolute collecting duct reabsorption was also greater in the albumin studies, 0.55 vs. 0.21 neq/min (P < 0.001), which could totally account for the difference in urinary sodium excretion between the two groups. (22)Na recovery in the final urine after end distal microinjections was 71% during Ringer's infusion and 34% during albumin (P < 0.001). From these data we conclude that: (a) Ringer's solution has a greater inhibitory effect on proximal tubular sodium reabsorption, and (b) in spite of this effect, differences in mucosal to serosal collecting duct sodium transport are primarily responsible for the greater natriuresis during Ringer's infusion.

Mechanism of the redistribution of renal cortical blood flow during hemorrhagic hypotension in the dog.

Studies were performed to define the mechanisms involved in the redistribution of renal cortical blood flow to inner cortical nephrons which occurs during hemorrhagic hypotension in the dog. The radioactive microsphere method was utilized to measure regional blood flow in the renal cortex. Renal nerve stimulation decreased renal blood flow 40% but had no effect on the fractional distribution of cortical blood flow. Pretreatment with phenoxybenzamine, phentolamine, propranolol, or atropine did not alter the redistribution of cortical flow during hemorrhage. A reduction in renal perfusion pressure by aortic constriction caused a qualitatively similar alteration in regional blood flow distribution as occurred during hemorrhage. When perfusion pressure was kept constant in one kidney by aortic constriction followed by hemorrhage, no redistribution occurred in the kidney with a constant perfusion pressure while the contralateral kidney with the normal perfusion pressure before hemorrhage had a marked increase in the fractional distribution of cortical flow to inner cortical nephrons. Additionally, retransfusion had no effect on the fractional distribution of flow in the kidney in which perfusion pressure was maintained at the same level as during hemorrhage while in the contralateral kidney in which pressure increased to normal there was a redistribution of flow to outer cortical nephrons. These studies indicate that the redistribution of renal cortical blood flow which occurs during hemorrhage is not related to changes in adrenergic activity but rather to the intrarenal alterations which attend a diminution in perfusion pressure.