Colocalization of collagen overexpression and inflammatory cell infiltration in the two-kidney one-clip rat model from the early days of hypertension onward

In the first 6 days of hypertension, infiltrated mononuclear cells were colocalized with collagen (I) mRNA-overexpressing fibroblasts in the adventitial area of unclipped kidney. The number of adventitial infiltrated mononuclear cells was correlated with adventitial collagen (I) surface expansion. After 22 days of hypertension no collagen (I) mRNA-overexpressing fibroblasts or any increase in collagen area or mononuclear cell infiltration was observed. In the interstitium of unclipped kidney, collagen (I) mRNA overexpression, collagen (I) expansion and mononuclear cell infiltration began later, from the 7th day of hypertension, and kept increasing. In the clipped kidney, after expansion in the first 6 days of hypertension, the adventitial collagen remained stable. These results suggest that in the unclipped kidney fibroblastic activation begins within the first 6 days of hypertension in the adventitial area, but is transient, and fibrosis then spreads in the intersitium. Mononuclear cell infiltration is colocalized and correlated with adventitial and interstitial fibrosis. In the first 6 days, hypertension is not the only cause of fibrosis; the same level of adventitial fibrosis is detected in the nonhypertensive clipped kidney. All observed pathological phenomena could be detected within the first 3 days of hypertension tubular lesions, vascular and interstitial fibrosis, and interstitial infiltration by mononuclear cells have all been well documented in HNS [9, 14, 24, 27, 41]. Nevertheless, the early cellular and fibrotic changes leading to HNS are still poorly understood. We have used the two-kidney one-clip (2K1C) as a model of HNS [41] to evaluate several phenomena appearing in the cortex during the first 31 days of high blood pressure (HBP). Collagen expansion around interlobular arteries and arterioles in the clipped and unclipped kidneys was quantified by morphometric analysis. Interstitial fibrosis, and mononuclear cell infiltration around arteries and arterioles in the unclipped kidney were quantitatively or semiquantitatively assessed. Cells synthesizing mRNAs for al collagen (I) and (IV) were located in the unclipped kidney by in situ hybridization.