On slip of a viscous fluid through proximal renal tubule with linear reabsorption

<p>The hydrodynamical problem of flow in proximal renal tubule is investigated. Axisymmetric flow of viscous, incompressible fluid through the proximal renal tubule that undergoes linear reabsorption with slip at the wall is considered. The stream function is used to transform the governing equations to system of ordinary differential equations. The analytical solutions for velocity components, pressure distribution, fractional reabsorption and the shear stress are found. The effect of slip parameter and reabsorption rate on the flow have been investigated. The points of extreme values for the axial and radial velocity components are identified. The solution is applied to physiological data from human and rat kidney, and the results are presented in tables and graphs.</p>

Enhanced renal Na+ reabsorption by carbohydrate in beverages during restitution from thermal and exercise-induced dehydration in men

We examined whether carbohydrate in beverages accelerated fluid retention during recovery from thermal and exercise-induced dehydration and whether it was caused in part by an enhanced renal Na+ reabsorption rate due to insulin secretion. After dehydrating by ∼2.3% body weight by exercise in a hot environment, seven young men underwent high-carbohydrate, low-carbohydrate, or control rehydration trials by drinking one of three beverages with 3.4 g glucose + 3.1 g fructose, 1.7 g glucose + 1.6 g fructose, or 0.0 g glucose + 0.0 g fructose per deciliter, respectively, in a common composition of electrolyte solution: 21 meq/l [Na+], 5 meq/l [K+], 16.5 meq/l [Cl−], 10 meq/l [citrate−3]. They drank the same amount of beverage as total body weight loss within 30 min. During the 60 min before the start of drinking and the following 180 min, we measured plasma volume (PV), plasma glucose ([Glc]p), serum insulin ([Ins]s), plasma Na+ concentrations, and the renal clearances of inulin, lithium, and Na+ with plasma vasopressin ([AVP]p) and aldosterone concentrations ([Ald]p) every 30 min. After dehydration, PV decreased by ∼5% and plasma osmolality increased by ∼6 mosmol/kgH2O in all trials with no significant differences among them. We found in the high-carbohydrate trial that 1) PV increased faster than in the control trial and remained at the higher level than other trials for the last 60 min ( P < 0.05); 2) accumulated urine volume was smallest after 90 min ( P < 0.05); 3) the renal Na+ reabsorption rate was greatest for the first 120 min ( P < 0.05); 4) during which period [AVP]p and [Ald]p were not significantly different from other trials (both, P > 0.9); and 5) [Glc]p and [Ins]s were highest from 45 to 105 min ( P < 0.05) during rehydration. Thus carbohydrate in beverages enhances renal Na+ reabsorption, and insulin is possibly involved in this enhancement.

Na+ secretion rate increases proportionally more than the Na+ reabsorption rate with increases in sweat rate

The purpose of this study was to measure the in vivo Na+ secretion and Na+ reabsorption rates of the human eccrine sweat gland with increases in sweat rate. Such data should help to elucidate the physiological mechanism responsible for the previously reported linear relationship between increases in sweat rate and Na+ concentration in sweat. On 5 days, each subject ( n = 10) completed a 30-min exercise bout in an environmental chamber set at 35°C and 40% relative humidity. The intensity for the five exercise bouts in the heat was set to approximate 50, 60, 70, 80, and 90% of age-predicted maximum heart rate. Forearm sweat samples and capillary blood samples were collected during each of the five 30-min exercise bouts. The sweat and blood samples were analyzed for Na+ concentration in sweat and serum, which were used to calculate the rate of Na+ secretion and Na+ reabsorption. The mean correlation between sweat rate and Na+ concentration in sweat was found to be r = 0.73. Within the sweat rate range of the present study, both Na+ secretion rate and Na+ reabsorption rate increased linearly; however, the Na+ secretion rate increased almost twice as fast (slope = 141 vs. 80). Thus the rate at which Na+ escaped reabsorption increased with increases in sweat rate and was significantly ( P < 0.05) correlated to the Na+ concentration in sweat (mean r = 0.90). Such results strongly suggest that the physiological mechanism responsible for the previously reported linear increase in Na+ concentration in sweat seen with increases in sweat rate is that the Na+ secretion rate increases proportionally more than the Na+ reabsorption rate.

Role of endogenously secreted angiotensin II in the CO2-induced stimulation of HCO3 reabsorption by renal proximal tubules

Previous studies demonstrated that the proximal tubule (PT) responds to isolated increases in basolateral ([CO2]BL) or “bath” CO2 concentration by increasing the HCO3− reabsorption rate ( J[Formula: see text]). Blockade of the rabbit apical AT1 receptor or knockout of the mouse AT1A receptor eliminates these effects, demonstrating a requirement for luminal ANG II that the PT itself synthesizes. In the present study, we examined the effects of the ACE inhibitor lisinopril on J[Formula: see text] in isolated perfused rabbit PTs (S2 segment), using out-of-equilibrium solutions to make isolated changes in [CO2]BL at a fixed baseline HCO3− concentration of 22 mM and fixed baseline pH of 7.4. Adding 60 or 240 nM lisinopril (in vitro Ki: 0.5 or 1.2 nM) to the lumen had no effect. These results are not consistent with the hypothesis that the PT secretes either angiotensinogen or ANG I. However, adding 60 nM basolateral lisinopril significantly decreased J[Formula: see text] at a [CO2]BL of 20%. Moreover, 240 nM basolateral lisinopril decreased baseline (i.e., at 5% CO2) J[Formula: see text] by one-half and completely eliminated the response to altering [CO2]BL from 0 to 20%, but left intact the stimulatory effect of 10−11 M basolateral ANG II. At extremely high concentrations (i.e., 100 μM), luminal lisinopril replicated the effects of 240 nM basolateral lisinopril. Our data are consistent with the hypothesis that lisinopril readily crosses the basolateral (but not apical) membrane to block ACE in a vesicular compartment. We conclude that the isolated PT predominantly secretes preformed ANG II, rather than angiotensinogen or ANG I.

Role of the AT1A receptor in the CO2-induced stimulation of HCO3− reabsorption by renal proximal tubules

The proximal tubule (PT) is major site for the reabsorption of filtered HCO3−. Previous work on the rabbit PT showed that 1) increases in basolateral (BL) CO2 concentration ([CO2]BL) raise the HCO3− reabsorption rate ( JHCO3), and 2) the increase that luminal angiotensin II (ANG II) produces in JHCO3 is greatest at 0% [CO2]BL and falls to nearly zero at 20%. Here, we investigate the role of angiotensin receptors in the [CO2]BL dependence of JHCO3 in isolated perfused PTs. We found that, in rabbit S2 PT segments, luminal 10−8 M saralasin (peptide antagonist of ANG II receptors), lowers baseline JHCO3 (5% CO2) to the value normally seen at 0% in the absence of inhibitors and eliminates the JHCO3 response to changes in [CO2]BL. However, basolateral 10−8 M saralasin has no effect. As with saralasin, luminal 10−8 M candesartan (AT1 antagonist) reduces baseline JHCO3 and eliminates the [CO2]BL dependence of JHCO3. Luminal 10−7 M PD 123319 (AT2 antagonist) has no effect. Finally, we compared PTs from wild-type and AT1A-null mice of the same genetic background. Knocking out AT1A modestly lowers baseline JHCO3 and, like luminal saralasin or candesartan in rabbits, eliminates the JHCO3 response to changes in [CO2]BL. Our accumulated evidence suggests that ANG II endogenous to the PT binds to the apical AT1A receptor and that this interaction is critical for both baseline JHCO3 and its response to changes in [CO2]BL. Neither apical AT2 receptors nor basolateral ANG II receptors are involved in these processes.

Effects of angiotensin II on the CO2 dependence of HCO3− reabsorption by the rabbit S2 renal proximal tubule

Previous authors showed that, at low doses, both basolateral and luminal ANG II increase the proximal tubule's HCO3− reabsorption rate ( JHCO3). Using out-of-equilibrium CO2/HCO3− solutions, we demonstrated that basolateral CO2 increases JHCO3. Here, we examine interactions between ANG II and CO2 in isolated, perfused rabbit S2 segments. We first used equilibrated 5% CO2/22 mM HCO3−/pH 7.40 in bath and lumen. At 10−11 M, basolateral (BL) ANG II increased JHCO3 by 41%, and luminal ANG II increased JHCO3 by 35%. At 10−9 M, basolateral ANG II decreased JHCO3 by 43%, whereas luminal ANG II was without effect. Second, we varied [CO2]BL from 0 to 20% at fixed [HCO3−]BL and pHBL. Fractional stimulation produced by BL 10−11 M ANG II falls when [CO2]BL exceeds 5%. Fractional inhibition produced by BL 10−9 M ANG II tends to rise when [CO2]BL exceeds 5%. Regarding luminal ANG II, fractional stimulation produced by 10−11 M ANG II fell monotonically as [CO2]BL rose from 0 to 20%. Fractional inhibition produced by 10−9 M ANG II rose monotonically with increasing [CO2]BL. Viewed differently, ANG II at 10−11 M tended to reduce stimulation by CO2, and at 10−9 M, produced an even greater reduction. In conclusion, the mutual effects of 1) ANG II on the JHCO3 response to basolateral CO2 and 2) basolateral CO2 on the JHCO3 responses to ANG II suggest that the signal-transduction pathways for ANG II and basolateral CO2 intersect or merge.

Flash photolysis of caged nitric oxide inhibits proximal tubular fluid reabsorption in free-flow nephron

A nonobstructing optical method was developed to measure proximal tubular fluid reabsorption in rat nephron at 0.25 Hz. The effects of uncaging luminal nitric oxide (NO) on proximal tubular reabsorption were investigated with this method. Proximal fluid reabsorption rate was calculated as the difference of tubular flow measured simultaneously at two locations (0.8–1.8 mm apart) along a convoluted proximal tubule. Tubular flow was estimated on the basis of the propagating velocity of fluorescent dextran pulses in the lumen. Changes in local tubular flow induced by intratubular perfusion were detected simultaneously along the proximal tubule, indicating that local tubular flow can be monitored in multiple sites along a tubule. The estimated tubular reabsorption rate was 5.52 ± 0.38 nl·min−1·mm−1 ( n = 20). Flash photolysis of luminal caged NO (potassium nitrosylpentachlororuthenate) was induced with a 30-Hz UV nitrogen-pulsed laser. Release of NO from caged NO into the proximal tubule was confirmed by monitoring intracellular NO concentration using a cell-permeant NO-sensitive fluorescent dye (DAF-FM). Emission of DAF-FM was proportional to the number of laser pulses used for uncaging. Photolysis of luminal caged NO induced a dose-dependent inhibition of proximal tubular reabsorption without activating tubuloglomerular feedback, whereas uncaging of intracellular cGMP in the proximal tubule decreased tubular flow. Coupling of this novel method to measure reabsorption with photolysis of caged signaling molecules provides a new paradigm to study tubular reabsorption with ambient tubular flow.