Progression of Glomerular Filtration Rate Reduction Determined in Conscious Dahl Salt-Sensitive Hypertensive Rats

Abstract

Sequential changes in glomerular filtration rate (GFR) during development of hypertension in the conscious Dahl salt-sensitive (SS) rat were determined using a new method for measurement. Utilizing a miniaturized device, disappearance curves of fluorescein isothiocyanate (FITC)-sinistrin were measured by transcutaneous excitation and real time detection of the emitted light through the skin. Rats with implanted femoral venous catheters (dye injection and sampling) and carotid catheters (mean arterial pressure (MAP) by telemetry) were studied while maintained on a 0.4% NaCl diet and on days 2,5,7,14 and 21 after switching to 4.0% (HS) diet. A separate group of rats were maintained on 0.4% for 21 days as a time control. MAP rose progressively from the last day of 0.4% (130±2 mmHg) reaching significance by day 5 of HS and averaged 162±7 mmHg by day 21. Urine albumin excretion was significantly elevated (3×) by day 7 of HS in SS rats. GFR became reduced on day 14 of HS falling from 1.53±0.06 ml/min/100g bwgt to 1.27±0.04. By day 21, GFR had fallen 28% to 1.1±0.04 ml/min/100g bwgt (t1/2 28.4±1.1 min.) No significant reductions of creatinine clearance (Ccre) were observed throughout the study in response to HS demonstrating the insensitivity of Ccre measurements even with creatinine measured using mass spectrometry. We conclude that the observed reduction of GFR was a consequence and not a cause of the hypertension and that this non-invasive approach could be used in these conscious SS rats for a longitudinal assessment of renal function.

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

“…Although it has been recognized that GFR is reduced in SS rats fed a high-salt diet, until recently it has been unknown whether an early reduction of GFR was importantly involved in the initiation of the hypertension or was a consequence of the hypertension. This question has recently been resolved by a study utilizing novel techniques to determine the progression of phenotypic changes that occur in SS rats when switched from a diet containing 0.4% NaCl to that of 4.0% (35), as shown in Fig. 8.…”

Renal Angiotensin-Converting Enzyme Is Essential for the Hypertension Induced by Nitric Oxide Synthesis Inhibition

“…GFR is calculated using (1) the half-life derived from the rate constant (a2) of the single exponential phase of the FITC-sinistrin excretion curve and (2) a semiempirical conversion factor, as validated in rats and mice. 21,37 This approach has several advantages over more traditional methods: It is less invasive, is not subject to confounding effects of anesthesia, and does not require terminal surgery. A miniaturized device (NIC-Kidney; Mannheim Pharma & Diagnostics, Mannheim, Germany) is fixed on the previously shaved back of the mouse.…”

“…The device is equipped with two light-emitting diodes that transcutaneously excite FITC-sinistrin at 480 nm and a photodiode to detect the emitted light signal at 521 nm. 21,37 The general protocol consisted of a resting baseline period of 10 minutes, after which FITCsinistrin was injected through the retro orbital sinus (15 mg/100 g body wt, dissolved in 0.1 ml sterile saline solution). For this procedure, mice were briefly anesthetized with inhalatorial isoflurane.…”

“…Data are collected (60 measurements/min) and stored in the internal memory of the microcontroller. 21,37 After collection, the device was detached from the mouse and the data were retrieved.…”

Role of Rho GDP Dissociation Inhibitor α in Control of Epithelial Sodium Channel (ENaC)-mediated Sodium Reabsorption

“…SS rats are a salt-sensitive strain that develops hypertension when fed a high salt diet. To investigate the effect of high salt consumption in these rats, chronic blood pressure monitoring in 8-week-old animals was performed using Data Sciences International (New Brighton, MN) telemetry as previously described (34). After transmitter implantation the rats were allowed to recover for at least 3 days.…”