Granger, Joey P.

Abstract The sections in this article are: Intrarenal Hemodynamic Control of Sodium Excretion Effects of Peritubular Starling Forces on Sodium Excretion Effects of Medullary Blood Flow on Sodium Excretion Effects of Renal Perfusion Pressure on Sodium Excretion Neural Control of Sodium Excretion Sodium Intake and Body Fluid Volumes Low‐Pressure Baroreceptors Renal Sympathetic Nerve Activity Hormonal Control of Sodium Excretion Renin–Angiotensin–Aldosterone System Renal Prostaglandin System Renal Kallikrein–Kinin System Natriuretic Hormone Atrial Natriuretic Peptide Summary

Renal interstitial hydrostatic pressure (RIHP) has been implicated in the regulation of sodium excretion. Studies using vasodilators and other maneuvers to increase RIHP have found a significant correlation between RIHP and sodium excretion. Since correlative studies do not prove a cause-and-effect relationship, it is not known whether the rise in sodium excretion in these studies is the result of increases in RIHP or if RIHP is elevated as a result of decreases in sodium and water reabsorption and increases in intratubular pressure. Therefore, the purpose of the present study was to determine whether elevation of intratubular hydrostatic pressures in response to direct inhibition of tubule transport with loop diuretics results in increases in RIHP in dogs and rats. Intrarenal hydrostatic pressures, renal hemodynamics, and sodium and water excretion were examined in dogs during intravenous administration of furosemide (3 mg/kg bolus followed by 0.03 mg.kg-1 x min-1) or bumetanide (60 micrograms/kg bolus followed by 1 microgram.kg-1 x min-1). Furosemide administration increased urinary flow rate (V; 0.10 +/- 0.02 to 4.6 +/- 0.97 ml/min), urinary sodium excretion (UNaV; 16 +/- 5 to 549 +/- 123 mu eq/min), and proximal tubule hydrostatic pressure (PT; 21 +/- 1 to 28 +/- 1 mmHg) but had no effect on RIHP (7.2 +/- 0.6 to 7.4 +/- 0.7 mmHg) or peritubular capillary hydrostatic pressure (14 +/- 1 to 14 +/- 1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

This study examined the effect of increases in renal interstitial hydrostatic pressure (PI) on sodium excretion (UNaV) utilizing a direct technique for increasing renal interstitial volume. PI was increased by renal interstitial volume expansion (RIVE) via injection of 50 microliters of a 2% albumin in saline solution into the renal interstitium through a chronically implanted interstitial catheter. RIVE resulted in a stable increase in PI (4.6 +/- 0.4 to 9.4 +/- 0.8 mmHg) that was sustained over a 30- to 40-min period without significant changes in renal blood flow or glomerular filtration rate. Increases in PI were associated with significant increases in urine flow (13.8 +/- 3.4 to 31.7 +/- 5.0 microliters/min) and UNaV (2.3 +/- 0.6 to 6.2 +/- 1.1 micro eq/min) and fractional excretion of Na (2.6 +/- 0.8 to 6.9 +/- 1.5%). To determine the importance of albumin in maintaining an elevated PI, the effects of renal interstitial injections of saline were compared with albumin in saline solution. Injection of 50 microliters of saline into the renal interstitium had no sustained effect on PI. Injection of 2% albumin in saline solution in the same group of rats resulted in significant elevations in PI and UNaV. These data indicate that direct increases in PI via renal interstitial volume expansion result in significant increases in UNaV, thus supporting a role for PI in controlling UNaV.

Previous studies have shown that renal interstitial volume expansion (RIVE) increases renal interstitial hydrostatic pressure and urinary sodium excretion. In the present study we investigated whether blockade of prostaglandin synthesis inhibits the increase in fractional sodium excretion induced by RIVE. Expansion of the renal interstitial volume was achieved by injecting 50 microliters of 2.5% albumin solution into a polyethylene matrix chronically implanted in the left kidney. Fractional sodium excretion (FENa), renal interstitial hydrostatic pressure (PI), and urinary prostaglandin excretion (UPGE2) were measured before and after RIVE in eight control, seven meclofenamate-treated, and eight indomethacin-treated rats. RIVE in the control animals resulted in significant increases in PI (delta + 4.2 +/- 0.8 mmHg), in FENa (delta + 1.02 +/- 0.27%), and in UPGE2 (% delta + 150 +/- 38%) without significant changes in glomerular filtration rate. Inhibition of prostaglandin synthesis with meclofenamate or indomethacin attenuated the natriuretic response and blocked the increase in UPGE2 associated with RIVE. In summary, direct increases in renal interstitial hydrostatic pressure increase UPGE2 and urinary sodium excretion. This natriuretic response is markedly diminished by inhibition of prostaglandin synthesis. These studies suggest that prostaglandin synthesis may have an important role in mediating the natriuretic effect of increased renal interstitial hydrostatic pressure during renal interstitial volume expansion.

The objective of the present study was to examine the effect of direct expansion of the renal interstitial volume on sodium reabsorption by proximal tubules of superficial and deep nephrons in the absence of systemic extracellular volume expansion. Renal interstitial volume expansion was achieved by injection of 50 microliter of 2.5% albumin in 0.9% saline into the renal interstitium via a polyethylene matrix that was chronically implanted in the interstitium of the rat kidney. Renal interstitial volume expansion increased renal interstitial hydrostatic pressure from 3.8 +/- 0.5 to 6.8 +/- 1.1 mmHg, P less than 0.05 (n = 5 rats). Fractional reabsorption of sodium by the superficial late proximal tubule decreased from 45.7 +/- 5.6 to 34.2 +/- 5.4%, P less than 0.05, and by the proximal tubule and descending limb of Henle's loop of deep nephrons it decreased from 73.9 +/- 2.9 to 57.2 +/- 6.3%, P less than 0.05 (n = 8 rats). Thus expansion of the renal interstitial volume increased renal interstitial hydrostatic pressure and decreased sodium reabsorption by the proximal tubules of superficial and deep nephrons.