Hypertension frequently accompanies chronic glomerulonephritis. Mesangial injury and glomerulosclerosis are common in glomerulonephritis and are often harbingers of progressive glomerular destruction. Thus, in a model of mesangial immune injury we studied the relationship between hypertension, mesangial injury, and glomerulosclerosis. We induced mesangial ferritin-antiferritin immune complex disease (FIC) in Dahl salt-sensitive (S) and salt-resistant (R) rats. S and R rats with FIC were fed chow containing 0.3% NaCl until 14 weeks of age and then switched to 8.0% NaCl chow until 28 weeks of age. Groups of control S and R rats (no FIC) were either fed 0.3% NaCl for 28 weeks or switched to 8.0% NaCl chow at 14 weeks of age. Blood pressure, serum creatinine, urinary protein, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined at 14 and 28 weeks of age. R rats with or without FIC did not develop hypertension; mesangial injury was minimal. At 14 weeks of age, only S FIC rats developed hypertension, proteinuria, significant mesangial expansion and early glomerulosclerosis. At 28 weeks of age, proteinuria, mesangial expansion, and glomerulosclerosis were significantly more severe in hypertensive S rats with FIC than in those without FIC. These studies show that despite a normal salt intake, mesangial injury hastened the onset of hypertension, but only in rats genetically predisposed to hypertension (S FIC at 14 weeks). High dietary salt further aggravated hypertension, which, in turn, magnified both mesangial injury and glomerulosclerosis. Clinically, the different rates of progression of human glomerulonephritis associated with hypertension may be in part dependent on similar mechanisms.

Accurate continuous chronic measurements of blood pressure from conscious laboratory rats are critical to many experimental protocols but have been difficult or impossible to acquire. A system consisting of an implantable radio-telemetry device, receiver, and computer-based data acquisition system that allows such measurements to be easily obtained has been developed. This system is capable of monitoring and recording arterial pressure (waveform, systolic, diastolic, and mean), heart rate, and activity from rats weighing greater than 175 gm for periods in excess of 6 months. Chronic patency has been achieved through a patented design which includes an antithrombogenic film and a gel membrane located at the catheter tip. Validation of telemetered measurements via carotid catheter has demonstrated the accuracy to be better than +/- 5 mmHg in 85% (N = 20) tested at 3 weeks post implantation, 86% (N = 15) tested at 8 weeks, and 78% (N = 9) at 12 weeks. Incidence of loss of patency was 2.3% (N = 44). This system has a demonstrated ability to obtain accurate continuous chronic measurements of arterial pressure free of the stressors associated with conventional systems.

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1. single nephron pressures, flows and resistances were studied in 17-18 week old genetically hypertensive and normotensive Kyoto rats resembling one another in renal total filtration rate, morphology and number of glomeruli in the kidney.2. Glomerular capillary pressures were similar Introduction in the two groups; however, the hypertensive rats had lower pressures at the end of the efferent Genetic factors play an important in the arteriole than did the normotensive development of essential and experimental hyper-Nephron filtration rates were similar in both tension (Dahl, Heine & Tassinary, 1962;Okamoto

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Blood pressure (BP) varies based on genetic and environmental factors. To test genetic and environmental influences on body weight (BW) and BP, one-cell homozygous embryos were transferred into spontaneously hypertensive (SHR, pup:shr) or (Wistar-Kyoto normotensive [WKY], pup:wky) normotensive rats' oviducts (embryos: s,w; oviduct-uterine: S,W), cross-suckled at birth (nurses S,W) and weaned to normal diets at day-21. BP at day-120 was measured by radiotelemetry and analyzed by methods of linear least square rhythmometry and analysis of variance. Genetics dominantly affected shr BP, causing it to be significantly higher at birth (24.6 ± 1.8 in sS versus 21.8 ± 1.7 mmHg in wW, P < 0.005), and at day-120 (198 ± 0.5 in sSS versus 127 ± 0.2 mmHg in wWW, P < 0.001), with lower BW than those of wky (5.3 ± 0.2 versus 5.7 ± 0.2 g at birth, 332 ± 5 versus 404 ± 6 g at day-120, both P < 0.001). Surprisingly, uterine-suckling milieus lowered shr BP significantly at day-120 (198 ± 0.5 in sSS versus 178 ± 0.5, 147 ± 0.6, 179 ± 0.5 mmHg in sSW, sWS, sWW, respectively, all P < 0.01). BP was slightly elevated when wky-genetics were implanted into the S-uterine by 4 mmHg (wSW, P < 0.05), whereas implanting shr embryos into the W-uterine environment (sWS) lowered BP by 51 mmHg (P < 0.001). In summary, the hypertensive shr-strain showed significantly lower BP when provided with an WKY-uterine environment and/or by WKY-nursing mothers, indicating that environment can modify genetic influences; yet the shr MESORs (rhythm-adjusted 24-h mean: midline estimating statistic of rhythm) lowered by WKY environments remained above MESORs encountered in wky-donors.

We investigated the role of the aldose reductase pathway in the pathogenesis of the nephropathy of rats with sever (non-insulin-treated) streptozocin-induced diabetes of 6 mo duration. The initial experiment included four groups of rats: diabetic and control animals on a 20% protein diet, which were untreated or treated with sorbinil (an aldose reductase inhibitor). Food intake was increased by diabetes but was uninfluenced by sorbinil, whereas urinary urea nitrogen excretion was increased and body weight was decreased by both variables. Glomerular basement membrane (GBM) width was increased by diabetes and decreased by sorbinil. No other structural changes were noted. We speculated that sorbinil could have slowed the abnormal rate of GBM thickening in diabetic rats and the normal increase in GBM width in control rats by inducing a mild catabolic state. The second experiment also involved four groups of rats: diabetic and control animals on a 50% protein diet, which were untreated or treated with sorbinil. In these studies, diabetes was again associated with reduced body weight, but sorbinil had no influence on urinary urea nitrogen. Urinary albumin excretion, which was increased by diabetes, was not affected by sorbinil. GBM width was increased by diabetes, but in contrast to animals on 20% protein diets, the animals on 50% protein diets and treated with sorbinil did not have reduced GBM widths. Mesangial volume fraction was greater in diabetic animals than in controls, and sorbinil largely prevented mesangial expansion in them. Surprisingly, the control animals on the 50% protein diet and given sorbinil had increased mesangial volume fraction compared with control rats on the same diet not given the drug.(ABSTRACT TRUNCATED AT 250 WORDS)