[Early matrix and cellular modifications in a hypertension model induced in rats (Goldblatt model). Quantitative and...

In the two-kidney one-clip hypertensive Goldblatt model of nephrosclerosis, the aim of this study was to detect, during the first twenty-eight days of high blood pressure, interstitial and periarterial (interlobular arterial and arteriolar) kidney changes. Morphometric analysis for type I collagen, in situ hybridization for type I and IV collagen mRNAs and immunohistochemistry for inflammatory cells were used to quantify and localize the following lesions: 1) A very early increase of collagen I proteins and mRNAs soon as the first 3 days and an important influx of inflammatory cells (macrophages and T-helper lymphocytes) were observed concomitantly. Then, these phenomenons decrease until the end of the experiment. 2) The interstitium reacts in the same way but with a lower intensity and with a time shifting. The main interstitial changes were seen after the second week of hypertension. 3) A same periarterial collagen I increase was measured during the first 3 days of hypertension in both clipped kidney and unclipped kidney. This hypertension-independent manifestation in the clipped kidney does not increase in later times of hypertension as it does in the unclipped kidney. A possible explanation is given by the angiotensin II concentration higher in the clipped kidney than in the unclipped kidney, and by direct angiotensin II effects as growth factor. 4) Periarterial fibrosis and macrophages or T-helper lymphocytes infiltration were co-localized. The intensity of both phenomenons is well correlated. These facts suggest that inflammatory cell infiltration and interstitial fibrosis are strongly and early linked.