Attenuated buffering of renal perfusion pressure variation in juxtamedullary cortex in SHR

Abstract

Renal tissue damage is substantially more pronounced in the juxtamedullary than in the superficial cortex in hypertensive rats, and the pathogenesis of the morphological changes are only partly understood. Glomerular capillary pressure (PGC) is increased, and steady-state autoregulation is normal in the deep renal cortex. We tested the hypothesis that the transient period from one pressure level to another may induce greater variation in local perfusion before stable autoregulation is established. An acute increase in local perfusion was compared in the superficial and juxtamedullary cortex of spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) after an abrupt increase in perfusion pressure. Total renal blood flow (RBF) was measured by a Transonic flow probe and local renal perfusion by laser Doppler flowmetry. Renal perfusion pressure was lowered to 50% of initial values and released abruptly. The maximal RBF increased from 6.3 ± 0.4 to a maximal value of 7.6 ± 0.3 ml/min ( P < 0.001) in SHR and from 7.3 ± 0.3 to 8.2 ± 0.6 ml/min ( P < 0.001) in WKY. These changes were not significantly different from each other. The change in superficial cortical perfusion was also not different between SHR and WKY. Pressure release increased juxtamedullary perfusion in SHR from 146 ± 8 to a maximal value of 228 ± 17 units ( P < 0.001) and in WKY from 160 ± 13 to 179 ± 11 units ( P < 0.001). The results were significantly different from each other ( P < 0.001). The time for maximal flow response was shorter in the deep cortex of SHR, and the time for normalization was longer than in WKY. These data indicate that the buffering of perfusion pressure variation is significantly attenuated in the juxtamedullary cortex, and significantly more so in SHR than in WKY, assuming a covariation of RBF and PGC, and this finding may explain the extensive morphological damage in the juxtamedullary cortex of SHR.

Glomerular and tubular damage in normotensive and hypertensive rats

“…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 where we found that autoregulation of renal blood flow (RBF) was less effective in hypertensive than in normotensive animals and less effective in inner than in outer cortex, i.e., pattern similar to that seen in glomerulosclerosis and tubular degeneration (27).…”

“…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 where we found that autoregulation of renal blood flow (RBF) was less effective in hypertensive than in normotensive animals and less effective in inner than in outer cortex, i.e., pattern similar to that seen in glomerulosclerosis and tubular degeneration (27).Proteinuria has been suggested to be the main pathogenic factor in tubular degeneration, whereas P GC and increased stretch are thought to be important in the development of the glomerulosclerosis. The primary intention of the present study was to conduct experiments to demonstrate a parallel progression of glomerulosclerosis and tubular damage in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).…”

“…In old SHR, degeneration was accompanied by proteinuria but no further increase of the P GC . Based on these observations, and our previous work on RBF autoregulation (15,18,27), we suggest that pressure variation in glomeruli and tubuli during every day pressure variation of the systemic blood pressure might play a pathogenetic role in development of glomerular and tubular degeneration in SHR.…”

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

“…This may relate to the observation that the intermediate segments of the interlobular artery in this strain exhibit an enhanced myogenic response (69), which would provide added protection for the distal superficial glomeruli but not the juxtamedullary nephrons. Autoregulatory responses are also reported to be slower in the juxtamedullary cortex of the aged SHR (127), and this could contribute to the pattern of injury. Finally, when autoregulatory capacity in the SHR is reduced by 5/6 renal ablation, these animals rapidly develop malignant nephrosclerosis (17).…”

Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk

“…Interestingly, it is reported that in SHRs, such transient changes in glomerular capillary pressure of the juxtamedullary nephron are much greater than in normotensive Wistar-Kyoto rats. 46 In addition, micropuncture studies have shown that only juxtamedullary (but not superficial) glomerular capillary pressure is elevated in SHR as compared with WKY, and this elevation becomes prominent in old SHRs. 31 Finally, it is reported that uninephrectomy causes selective deep nephron hyperfiltration in SHRs but not in WKY.…”