A highly sensitive oscillatory tubulo-glomerular feedback (TGF) response has previously been demonstrated in normotensive Sprague-Dawley rats. The purpose of the present study was to examine whether such as oscillating TGF-response could be elicited in Wistar-Kyoto rats (WKY) and genetically hypertensive rats (SHR) and furthermore if any differences in the TGF-response characteristics between SHR and WKY rats could be detected. The closed loop function of the TGF-system was studied. In 12-18-week-old WKY rats regular oscillations in the intratubular pressure occurred spontaneously. The median frequency were 29.7 mHz (range 20-46.7 mHz). In SHR rats, spontaneous oscillations also occurred, but these were highly irregular. Spontaneous oscillations were more frequent in WKY than in SHR (88% vs. 54%). In both strains, oscillations could be elicited by free flow microperfusion with artificial tubular fluid (ATF). When furosemide was added to the ATF in a concentration of 0.1 mM, the oscillations were abolished in both strains of rats. It is concluded that, in both strains of rats the oscillatory phenomena depend upon TGF activity. It is suggested that the irregular pattern of the oscillations observed only in SHR rats may represent a chaotic process.

Fractional lithium clearance (CLi/CIn), transit time-occlusion time (e-TT/OT), and late proximal tubular fluid-to-plasma inulin ratio [1/(TF/P)In] collected by micropuncture were determined successively in the same rat during Amytal anesthesia. The rats were examined during hydropenia, after partial aortic constriction, or during saline diuresis. There was a linear relationship (r = 0.80) between CLi/CIn and e-TT/OT. The 1/(TF/P)In ratio correlated closely with both CLi/CIn (r = 0.88) and e-TT/OT (r = 0.91) when intraluminal pressure was maintained at the free-flow level during fluid collection. If fluid collection was guided merely by the position of an oil droplet and the luminal diameter, the 1/(TF/P)In data were not correlated with either CLi/CIn or e-TT/OT. Over a wide range of proximal absolute and fractional reabsorption rates the technically simpler lithium clearance and TT/OT methods may provide data on proximal fractional reabsorption that are as accurate and reliable as data obtained by pressure-controlled micropuncture collection. Micropuncture carried out without pressure control provides highly inaccurate data and is clearly inferior to the other methods. These results are consistent with the possibility that lithium is reabsorbed exclusively by the proximal tubules, 17-20% being reabsorbed by the pars recta.

The Dahl salt-sensitive (Dahl S) rat develops hypertension and renal injuries when challenged with a high salt diet and has been considered to be a model of chronic renal failure. Renal injuries appear very early in life compared with the spontaneously hypertensive rat (SHR). During the course of hypertension, a gradual impairment of autoregulatory control of renal blood flow might expose the glomerular circulation to periods of elevated pressure, resulting in renal injuries in Dahl S rats. Dynamic autoregulatory capacity was assessed in Dahl S and Dahl salt-resistant (Dahl R) rats, SHR, and Sprague-Dawley rats by inducing broad-band fluctuations in the arterial blood pressure and simultaneously measuring renal blood flow. Dynamic autoregulation was estimated by the transfer function using blood pressure as the input and renal blood flow as the output. Renal morphological injuries were evaluated in Dahl S rats and SHR and were scored semiquantitatively. Dynamic autoregulation was efficient and comparable in the low-frequency range (<0.015 Hz) in Dahl R rats, SHR, and Sprague-Dawley rats. The response in Dahl S rats depended strongly on the initiation time of the high salt diet. Autoregulation was preserved during a low salt diet and in rats exposed to a late-onset hypertension of short duration, only partly preserved if the late-onset hypertension was of a longer duration, and abolished in early-onset hypertension. All Dahl S rats on a high salt diet showed severe morphological changes in the kidney. In conclusion, autoregulatory capacity in the kidney of Dahl S rats is gradually impaired when rats are rendered hypertensive with a high salt diet. Renal morphological injuries develop before loss of dynamic autoregulation. Impaired autoregulation appears to be the result, not the cause, of the process that ultimately leads to renal failure in the Dahl S rat.

We describe in gas anesthetized rats an oscillating intratubular pressure response, probably of vascular origin, sensitive to small physiological changes in fluid delivery to the distal tubule. The oscillation apparently indicates that an adjustment of vascular resistance is in operation, but at present it reveals neither the effector site (afferent and/or efferent arteriole) nor the effector mechanism (vasoconstriction and/or dilatation). The renin-angiotensin system seems to be involved in this phenomenon.

In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least 2 years or until they needed dialysis. The groups were comparable with respect to age and sex distribution, etiology of renal diseases, initial levels of renal function and arterial blood pressure (BP), and protein intake. The therapeutic goal was a BP of 120 to 140/80 to 90 mm Hg. The GFR, estimated by the plasma clearance of 51Cr-EDTA, was measured every third month, and the individual rate of progression was calculated as the slope of the GFR v time plot. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to -7.11) mL/min/1.73 m2/month and in the control group it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (P less than .05). There was no significant difference in blood pressure or plasma lipid levels between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy.

The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The present study was designed to test the effect of clamping plasma ANG II concentrations ([ANG II]) by simultaneous infusion of the angiotensin-converting enzyme inhibitor captopril and ANG II on RBF autoregulation in halothane-anesthetized Sprague-Dawley rats. Autoregulation was defined as the RBF response to acute changes in renal perfusion pressure (RPP). Regulation was defined as changes in RBF during long-lasting changes in RPP. The results showed that a prolonged reduction of RPP reset the lower limit of autoregulation from 85 +/- 1 to 73 +/- 2 mmHg (P < 0.05) and regulated RBF to a lower level. Reduction of RPP to just above the lower limit of autoregulation (88 mmHg) induced regulation of RBF to a lower level within 10 min. Clamping [ANG II] per se reset the lower limit of autoregulation to 62 +/- 5 mmHg. In this case, reduction in RPP to 50 mmHg did not induce a downregulation of RBF. We conclude that ANG II plays an important role in the resetting of the autoregulation limits. The ability to regulate RBF to a new level as a response to changes in RPP also depends on changes in [ANG II].

The effect of three cycles of high-dose cisplatin (40 mg/m2 day for 5 days) on renal tubular function was evaluated in 30 patients. A significant impairment of proximal tubular salt and water reabsorption rates was observed, but also distal tubular function seemed to be affected. These changes were also present 6 months after termination of treatment. Sodium and magnesium clearance increased significantly during treatment. Magnesium clearance normalized shortly after treatment but sodium clearance was significantly elevated 6 months after treatment. Proteinuria, albuminuria, and amino aciduria, together with an increase of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) excretion rates, were observed during each treatment cycle. A good correlation was registered between the increase in urinary excretion rates of protein, NAG, and magnesium and the decrease in proximal tubular salt and water reabsorption during cisplatin administration.

SUIMMARY1. Fluid transport rate and oxygen consumption (Qo2) were studied in rabbit gall-bladder preparations in vitro exposed on both sides to identical Ringer solutions with NaCl concentrations (and osmolarities) varying from 70 to 140 m-equiv Na+/l. (and 173-313 m-osmole/l.).2. The time sequence of acute effects on transport rate resulting from sudden changes in the NaCl concentration of the bathing solutions indicated that, (a) as a primary effect, fluid volume transfer rate remained unaffected whereas Na transport rate changed abruptly in direct proportion to the Na concentration of the bathing media; (b) a secondary, delayed and partly reversible depression of fluid transfer rate following elevation of the NaCl concentration was observed only when the rate of transport was relatively high initially. solutions, respectively. 5. Removal of K from the bathing solutions was followed by a gradual and partly reversible depression of fluid transport rate to a minimum level (about 100 x 10 4 #1 H20. min' . mg-') independent of the initial transport rate.6. It is concluded that the range of absorption rates of isosmotic fluid * Graduate student research scholar.0. FREDERIKSEN AND PAUL P. LE YSSAC from the gall-bladder lumen represents a range of energy requiring capacities for transfer of fluid volume units; the data suggest that the intracellular (cytoplasmic) ion composition, depending on the presence of external K, as well as hormonal action may influence the capacity of the transcellular fluid transport mechanism. 7. A model (a 'mechanical volume pump') for transcellular transfer of fluid volume units, allowing for flexible specificity with regard to the actively transported solutes, and requiring the presence of Na+ and Cl-, is proposed.