Proximal tubular function in transgenic mice overexpressing atrial natriuretic factor

A transgenic mouse model in which atrial natriuretic factor (ANF) expression is targeted to the liver was used to study intrarenal adjustments to the chronically elevated hormone level. Such animals, designated TTR-ANF, are characterized by reduced arterial blood pressure but similar sodium excretion compared with nontransgenic siblings. Proximal tubular micro-puncture gave the following results: single-nephron filtration rate = 12.7 ± 1.1 vs. 15.6 ± 1.9 nL/min (TTR-ANF versus nontransgenic, ns); end-proximal tubular fluid/plasma concentration ratio of inulin = 1.93 ± 0.09 vs. 1.97 ± 0.15 (ns); fractional reabsorption of sodium = 45.5 ± 2.8 vs. 46.0 ± 3.8% (ns); fractional reabsorption of chloride = 33.6 ± 3.3 vs. 32.4 ± 4.1% (ns). These data indicate that life-long elevation of plasma ANF concentration was not associated with significant alteration in single-nephron filtration rate and proximal tubular function. We conclude that compensatory anti-natriuretic mechanisms, localized downstream from the proximal tubule, can prevent ANF natriuresis.Key words: micropuncture, single-nephron filtration rate, sodium chloride reabsorption.

Effects of beta 1-adrenergic blockade on glomerular dynamics and angiotensin II response

Adrenergic activity regulates renal function by several mechanisms. Renal nerves not only exert vasoconstrictor functions but also may influence glomerular hemodynamics by beta-adrenergic activity, especially via the effects on renin angiotensin activity. Little is known of the specific glomerular hemodynamic alterations resulting from beta 1-adrenergic blockade. Current studies examined the effects of 4-6 days of treatment with atenolol (50 mg/kg), a beta 1-selective adrenergic antagonist, on glomerular hemodynamics in plasma volume-expanded Munich-Wistar rats. Atenolol treatment reduced blood pressure both in the awake state and during micropuncture. This reduction in blood pressure contributed to a decrease in nephron filtration rate (48 +/- 1 in untreated rats vs. 40 +/- 1 nl.min-1.g kidney wt-1 in the atenolol-treated group, P less than 0.05) by reduction in nephron plasma flow (182 +/- 2 vs. 154 +/- 4 nl.min-1.g kidney wt-1 in the atenolol-treated rats). No other determinant of glomerular ultrafiltration was influenced by atenolol treatment. Since beta 1-adrenergic blockade may influence the generation of angiotensin II, the response to angiotensin II infusion was assessed and found not to differ from control untreated animals. These studies demonstrate that beta 1-receptor blockade reduced nephron filtration rate by decreasing mean arterial blood pressure and nephron plasma flow without significant modifications in vascular resistance and the glomerular hydrostatic pressure gradient.

Adrenergic and angiotensin II influences on renal vascular tone in chronic sodium depletion

To examine the role of adrenergic activity on the reduction in nephron filtration rate during chronic sodium depletion in rats, we have measured all the determinants of glomerular ultrafiltration before and after acute unilateral renal denervation. We also examined whether this adrenergic influence was angiotensin II mediated by performing the same protocol with the addition of systemic infusion of an angiotensin-converting enzyme inhibitor, MK 421. The results indicate that both angiotensin II and adrenergic activity contribute to the maintenance of renal vascular resistance during chronic sodium depletion. Acute renal denervation restored nephron filtration rate in chronic sodium-depleted rats (27 +/- 1 to 32 +/- 2 nl/min, P less than 0.05) to control levels (33 +/- 1 nl/min) via reductions in afferent and efferent arteriolar resistances, which also increased nephron plasma flow (85 +/- 5 to 109 +/- 6 nl/min, P less than 0.05). Infusion of MK 421 also increased plasma flow in chronic sodium-depleted rats (116 +/- 11 nl/min, P less than 0.05) through decreases in both arteriolar resistances. Denervation in MK 421-treated rats further increased nephron plasma flow to 137 +/- 10 nl/min (P less than 0.05) only as a result of decreased afferent resistance. The findings indicate that the glomerular hemodynamic changes that characterize chronic sodium depletion are primarily due to the activity of angiotensin II. However, renal adrenergic activity contributes an independent effect on afferent resistance and an effect on efferent resistance via adrenergic effects on angiotensin II.

Measurement of nephron filtration in the dog: role of proximal intratubular pressure

Previous studies concerning the measurement of single nephron filtration rate have shown that collections of proximal tubular fluid, in which an oil drop is held in a constant position, do not affect intratubular pressure in the early proximal tubule in the hydropenic rat. Since intratubular pressures are higher in the dog than the rat, we investigated the effect of position-controlled collections on proximal pressure and single nephron filtration rate (SNGFR) in the dog. During position-controlled collections, early proximal pressure fell 5.8 +/- 0.9 mmHg and SNGFR was 76.3 +/- 5.3 nl/min. During proximal re-collections, in which proximal pressure was maintained near the free-flow value using a long immobile oil block, SNGFR was significantly less, 44.4 +/- 5.5 nl/min. For each micropunctured kidney, SNGFR was also estimated by dividing GFR by the number of glomeruli (mean, 5.4 +/- 0.5 X 10(5)). Estimated SNGFR (50.9 +/- 6.3 nl/min) was not significantly different from pressure-controlled SNGFR but was significantly less than position-controlled SNGFR. Accordingly, in the dog, early proximal pressure decreases during position-controlled collection of proximal tubular fluid, resulting in an overestimation of SNGFR. This artifact can be avoided by controlling the intratubular pressure during collection of tubular fluid.

Measurement of Single Nephron Filtration Rate in the Kidney of the River Lamprey, Lampetra Fluviatilis L

The reliability of [3H]inulin as a reference substance for the measurement of glomerular filtration rate (GFR) in river lampreys was investigated. Simultaneously measured renal clearances of [3H]inulin and [14C]-polyethylene glycol (PEG) were not significantly different. Recoveries of [3H]inulin in the urine following its injection into the proximal tubule and urinary duct averaged 83.5±4.0% (n = 14) and 93.0±4.6% (n = 9) respectively. No evidence was obtained to suggest penetration of the tubular wall by [3H]inulin following its introduction into peritubular capillaries. Gel-filtration of lamprey plasma and urine produced no signs of any significant degradation of the inulin to fructose. [3H]inulin recoveries, though significantly below 100% (P < 0.001), were considered adequate to justify its use after allowing for possible sources of error. A mean single nephron filtration rate (SNGFR) value of 7.02±0.27 nl/min (n = 89) was obtained from the kidneys of anaesthetized freshwater lampreys. [51Cr]EDTA was found to be totally unsuitable for the measurement of GFR in this species.

Determinants of proximal tubular reabsorption as mechanisms of glomerulotubular balance

The determinants of absolute proximal reabsorption (APR) were studied in four groups of rats during hydropenia, partial renal vein occlusion (RVO), saline expansion, and RVO after saline expansion. Nephron filtration rate (SNGFR), nephron plasma flow (RPF), APR, and proximal tubule (Pt) peritubular capillary (HPc), and interstitial (HPi) hydrostatic pressures were measured by micropuncture techniques. Subcapsular space (pii) and star peritubular capillary (piE) oncotic pressures were also determined. The peritubular capillary permeability coefficiency (LpAR) and the corresponding effective reabsorptive pressure (ERP) were computed, where APR = LpAR . ERP, and ERP = net reabsorptive pressure across the peritubular capillary. The results indicate that APR correlates best with SNGFR (P less than 0.05), but not with (pii - HPi), RPF, or LpAR. There was a significant relationship between piE and LpAR, where LpAR fell with increases in piE (P less than 0.01). In conclusion, 1) changes in absolute proximal reabsorption correlate best with changes in nephron filtration rate but not with (pii - HPi) across this range of values, 2) changes in efferent oncotic pressure (piiE) correlated inversely with LpAR, and 3) glomerulotubular balance in the proximal tubule can be partially attributed to intraluminal factors.