To gain insight into the mechanisms in the development of glomerulosclerosis in juxtamedullary cortex, the degree of glomerulosclerosis, glomerular tuft diameter, glomerular capillary pressure (Pgc), and local renal blood flow (RBF) autoregulation were measured in superficial and juxtamedullary cortex of 10- and 70-wk-old spontaneously hypertensive rat (SHR), using aged matched Wistar-Kyoto (WKY) rats as controls. Pgc was measured after corticotomy by direct micropuncture of glomeruli in superficial and juxtamedullary cortex. Total RBF was measured by a transit-time flowmeter (Transonic) and local blood flow by use of laser-Doppler flowmetry. The degree of glomerulosclerosis measured by a semiquantitative histological technique was significantly increased in juxtamedullary compared with superficial cortex in all groups. The difference was most pronounced in the juxtamedullary cortex of 70-wk-old SHR. Pgc was significantly increased in juxtamedullary cortex compared with superficial cortex in 70-wk SHR (57.1 ± 2.7 vs. 46.5 ± 0.5 mmHg, P < 0.01). The corresponding data set from 70-wk WKY was 45.5 ± 0.43 vs. 41.6 ± 1.5 ( P < 0.05). The Pgc in juxtamedullary cortex of 10-wk SHR was slightly higher than in superficial cortex (45.1 ± 2.3 vs. 50.1 ± 1.2 mmHg, P = 0.05), whereas there was no difference in 10-wk WKY. Glomerular diameter was larger in juxtamedullary cortex in old animals but not significantly different in 10-wk WKY rats and 10-wk SHR. Total RBF was reset to higher perfusion pressures in hypertensive rats. Juxtamedullary and superficial blood flow autoregulation were not significantly different from total RBF autoregulation in all groups. These results suggest that hypertrophy as well as increased Pgc might contribute to the development of manifest glomerulosclerosis. Changes in local blood flow autoregulation do not seem to play a major role in the development of glomerulosclerosis.

Renal blood flow (RBF) autoregulation was examined in untreated 10- and 40-wk-old spontaneously hypertensive rats (SHR) [mean arterial pressure (MAP) 125 +/- 4 and 167 +/- 7 mmHg] and in captopril-treated (7 days) 10- and 40-wk-old SHR (88 +/- 7 and 112 +/- 5 mmHg). Age-matched Wistar-Kyoto rats (WKY) were used as controls (MAP 91 +/- 3 and 104 +/- 2 mmHg). The study was carried out in rats with and without acute uninephrectomy. In 10-wk-old acutely uninephrectomized animals, the lower pressure limit of autoregulation was 78 +/- 4 mmHg in WKY, 102 +/- 5 mmHg in SHR (P less than 0.02), and 78 +/- 7 mmHg in captopril-treated SHR (P greater than 0.10). The renal vascular resistance (RVR) was significantly elevated at the lower pressure limit of RBF autoregulation in untreated SHR (P less than 0.02) but became normal after treatment (P greater than 0.10). Neither uninephrectomy nor variation of RBF between different batches seemed to influence the lower pressure limit of RBF autoregulation. In 40-wk-old acutely nephrectomized animals, the lower pressure limit of RBF autoregulation in WKY was 85 +/- 4 mmHg, 128 +/- 3 mmHg in SHR (P less than 0.001), and 101 +/- 5 mmHg in captopril-treated SHR (P less than 0.01). RVR at the lower pressure limit was increased in untreated SHR (P less than 0.01), but fell to normal values during captopril treatment. Neither the uninephrectomy nor variation of RBF between different batches of rats seemed to influence the lower pressure limit of RBF autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Tubular cell damage is an important mediator of interstitial fibrosis in chronic renal diseases. Glomerular and tubular damage in genetic hypertension was therefore studied. Tubular and glomerular damage was investigated in 10-, 40-, and 70-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and compared with glomerular capillary pressure (PGC) and glomerulosclerosis in superficial (OC) and juxtamedullary (JMC). Tubular vimentin was used as criterion of tubular damage. Variation in tubular diameter was measured during change in perfusion pressure, and ureter ligation was used to demonstrate the relationship between tubular pressure and appearance of vimentin-positive cells. Tubular and glomerular damage was most pronounced in JMC and greater in SHR than in WKY. It was absent in 10-wk-old WKY and significantly higher in JMC of SHR compared with WKY at 70 wk of age. Numbers of vimentin-positive segments were 18 Ϯ 9 vs. 38 Ϯ 7% in JMC of 70-wk-old WKY and SHR (P Ͻ 0.02), and glomerulosclerosis was seen in 8 Ϯ 3 vs. 19 Ϯ 5% of glomeruli in JMC of 70-wk-old WKY and SHR, respectively (P Ͻ 0.01). P GC was 45 Ϯ 3 mmHg in JMC of WKY and 57 Ϯ 3 mmHg in JMC of 70-wk-old SHR (P Ͻ 0.001). Tubular diameter variation was greatest in SHR (P Ͻ 0.05) during pressure variation. Proteinuria was present only in 40-and 70-wk-old SHR and did not correlate with tissue damage. Tubular and glomerular damage in both strains develops in parallel and may be caused by a common mechanism, which may be glomerular capillary and tubular wall stretch during acute blood pressure variation which is greatest in JMC in SHR.vimentin; sclerosis index; glomerular capillary pressure; proteinuria IN PROGRESSIVE HYPERTENSIVE disease, physical factors such as increased glomerular capillary pressure (P GC ), filtration rate, and flow are considered to be important mediators of glomerulosclerosis (15,21). Recent research has focused on other aspects, such as growth, tubular damage, accumulation of collagens, and appearance of immune cells in the peritubular interstitium. Altered tubular cell function seems to play a pivotal role in development of the tubulointerstitial pathology (25). In diseased kidneys, tubular cells may acquire macrophage-like attributes and synthesize complement, MCH class II molecules, actin of the smooth muscle cell type, growth factors, chemokines, and other cytokines, i.e., orchestrate a chronic immune process in the peritubular interstitium and disturb the balance of growth and structure (17,20,28).It is well documented that glomerulosclerosis in hypertension is greater in the deep than in the superficial cortex (11,22), and the tubular derangement in inner cortex is also more pronounced than in the outer cortex (24). In the hypertensive animal, proteinuia develops from juxtamedullary nephrons and P GC is higher in glomeruli in juxtamedullar than superficial glomeruli in hypertensive rats (11). The early development of juxtamedullary degeneration in hypertensive animals has also been supported by a recent study w...

Microspheres with diameters of from 10 to 30 mum were injected into the renal arteries of three anesthetized dogs. The six kidneys were studied by light microscopy. The diameters of the spheres trapped in the afferent arterioles and of all spheres recovered in the kidneys were recorded. On the basis of the distribution of diameters in these two populations of spheres, the average diameter of the afferent arteriole and the distribution of the afferent arteriolar diameters were estimated. The average diameter of the afferent arterioles was 16.3 mum (S.D. 2.2 mum), without any difference between three cortical layers of equal thickness. The mean diameter of spheres trapped in the interlobular arteries was 25.7 mum (S.D. 2.6). It is suggested that the pressure drop along some interlobular arteries may be of physiological importance, affecting the autoregulation of blood flow in the renal cortex.

Renal blood flow (RBF) autoregulation was examined in the clipped and nonclipped kidneys in two groups of two-kidney, one-clip (2K-1C) hypertensive rats 10 wk after clipping. The arterial pressure distal to the clip and the renin secretion rate (RSR) were also examined. The blood pressure (BP) was 149 +/- 4 and 162 +/- 6 mmHg in the two hypertensive groups vs. 114 +/- 3 mmHg in the controls (P less than 0.02). The RBF (in ml X min-1 X kidney-1) was 4.27 +/- 0.41 in the nonclipped and 2.18 +/- 0.23 in the clipped kidneys (P less than 0.001). The pressure distal to the clip was 104 +/- 7 mmHg. The renal vascular resistance (RVR) (in mmHg X ml-1 X min-1 X g-1) was 25.0 +/- 1.4 in the control kidneys vs. 58.4 +/- 4.5 in the nonclipped (P less than 0.001) and 39.9 +/- 6.6 in the clipped kidneys (P less than 0.01). The RBF autoregulation was well preserved in the nonclipped kidneys but reset to a higher lower pressure limit of autoregulation of 106 +/- 4 mmHg, which was significantly higher than in the normotensive controls (84 +/- 6 mmHg) (P less than 0.01). In the clipped kidneys there was complete loss of RBF autoregulation. RSR decreased with reduction of the perfusion pressure in the clipped kidneys. The increased RVR might have been due to a combination of structural and functional changes in both kidneys.