Lockhart, John C.

Increases in renal interstitial hydrostatic pressure (RIHP) increase urinary sodium excretion (UNaV). Experimentally increasing RIHP by direct renal interstitial volume expansion (DRIVE) has been shown to decrease proximal tubule sodium reabsorption. The purpose of the present study was to investigate whether the renin-angiotensin system modulates the natriuretic response to DRIVE. Unilateral nephrectomy and implantation of two polyethylene matrices were performed 3 wk before the acute experiment. Fractional sodium excretion (FENa), RIHP, and glomerular filtration rate (GFR) were measured before and after DRIVE in control rats (n = 9) and in rats receiving the angiotensin II (ANG II) receptor antagonist, losartan potassium (10 mg/kg i.v.; n = 10). DRIVE was achieved by infusing 100 microliters of 2.5% albumin solution directly into the renal interstitium. GFR remained unchanged by DRIVE in both groups. In control animals, DRIVE significantly increased both RIHP (delta 3.8 +/- 0.5 mmHg) and FENa (delta 0.92 +/- 0.19%). In the losartan-treated group, RIHP (delta 2.8 +/- 0.4 mmHg) and FENa (delta 1.93 +/- 0.41%) also significantly increased. The natriuretic response to DRIVE was significantly enhanced during ANG II receptor blockade compared with control animals (delta UNaV/delta RIHP = 2.01 +/- 0.67 vs. 0.44 +/- 0.17 mu eq.min-1 x mmHg-1, respectively; P < 0.05). These results suggest that the blockade of angiotensin enhances the natriuretic response to increased RIHP during DRIVE.

An increase in medullary blood flow has been implicated as a mediator of the natriuresis following increases in renal perfusion pressure (RPP). We examined whether administration of L-arginine, the substrate for nitric oxide production, restores the impaired vasa recta hemodynamic response to increases in RPP and the blunted pressure natriuresis of the spontaneously hypertensive rat (SHR). The response of descending (QDVR) and ascending vasa recta blood flow (QAVR) and of urinary sodium excretion (UNaV) was examined as RPP was increased by means of an adjustable aortic clamp placed above the renal arteries in young SHR and Wistar-Kyoto (WKY) rats. When RPP was increased in SHR receiving infusion of L-arginine (n = 7), QDVR and QAVR increased significantly in association with increases in UNaV. In SHR receiving the inactive enantiomer, D-arginine (n = 7), similar increases in RPP failed to increase QAVR and QDVR and were associated with an attenuated increase in UNaV. WKY animals infused with either D-arginine or L-arginine had increases in QDVR, QAVR, and UNaV in response to increases in RPP that were of similar magnitude to SHR receiving L-arginine. Thus the administration of L-arginine to SHR restores the pressure-dependent increases in renal medullary hemodynamics in association with restoration of pressure natriuresis.

This study investigated the role of volume status and perfusion pressure on the hemodynamic response of cortical and medullary renal capillaries to systemic inhibition of nitric oxide. NG-Monomethyl-L-arginine (L-NMMA) was infused intravenously (15-mg/kg bolus and 500-micrograms.min-1.kg-1 infusion), and blood flow in cortical capillaries (QCC) and in descending (QDVR) and ascending vasa recta (QAVR) was measured by fluorescence videomicroscopy in euvolemic and volume-expanded anesthetized Munich-Wistar rats. L-NMMA in euvolemic rats decreased vasa recta blood flow (delta QDVR, 3.97 +/- 0.80 nL/min [P < .01]; delta QAVR, 1.90 +/- 0.39 nL/min [P < .01]; n = 6) and QCC (delta QCC, 0.57 +/- 0.15 nL/min [P < .01]; n = 7) despite increases in renal perfusion pressure (RPP). Fractional excretion of sodium (FENa) remained unchanged. In volume-expanded rats, L-NMMA decreased vasa recta blood flow when RPP increased (delta QDVR, 1.42 +/- 0.79 nL/min [P = .05]; delta QAVR, 1.95 +/- 0.34 nL/min [P < .001]; n = 9) or was held constant by partial aortic occlusion (delta QDVR, 1.19 +/- 0.45 nL/min [P < .05]; delta QAVR, 1.44 +/- 0.40 nL/min [P < .01]; n = 8). QCC was unchanged by L-NMMA when RPP increased (delta QCC, 0.27 +/- 0.20 nL/min; n = 8) but decreased significantly by 0.61 +/- 0.11 nL/min (P < .01, n = 8) when increases in RPP were prevented. FENa increased when RPP increased (delta FENa, 2.47 +/- 0.51%; P < .001) and was held constant (delta FENa, 2.64 +/- 0.46%; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Pressure natriuresis may be mediated through increases in inner medullary vasa recta blood flow (QVR). By means of acute renal decapsulation to prevent increases in renal interstitial hydrostatic pressure (RIHP), the effect of increases in QVR in the presence and absence of changes in RIHP in the natriuretic and diuretic responses to increases in renal perfusion pressure (RPP) was evaluated. Blood flow in descending (QDVR) and ascending (QAVR) vasa recta was determined in the exposed papilla by fluorescence videomicroscopy in anesthetized euvolemic Munich Wistar rats. In rats with intact renal capsules (n = 12), increases in RPP from 101 +/- 0.5 to 132 +/- 2.9 mm Hg caused significant increases in QDVR (from 4.7 +/- 0.9 to 5.5 +/- 0.9 nl/min, p < 0.001) and QAVR (from 2.8 +/- 0.2 to 3.5 +/- 0.2 nl/min, p < 0.001) in association with increases in RIHP (from 4.6 +/- 1.3 to 7.6 +/- 1.3 mm Hg, p < 0.001), urine flow (from 16.2 +/- 2.6 to 20.2 +/- 3.2 microliters.min-1 x g kidney wt-1, p < 0.01), and urinary sodium excretion (from 2.10 +/- 0.38 to 3.36 +/- 0.62 mu eq.min-1 x g kidney wt-1, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)