Increased glomerular capillary pressure and size mediate glomerulosclerosis in SHR juxtamedullary cortex.

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.