Structural alterations of tight junctions are associated with loss of polarity in stroke-prone spontaneously hypertensive rat blood-brain barrier endothelial cells

The mechanisms leading to stroke in stroke-prone spontaneously hypertensive rats (SHRSP) are not well understood. We tested the hypothesis that the en dothelial tight junctions of the blood-brain barrier are altered in SHRSP p rior to stroke. We investigated tight junctions in 13-week-old SHRSP, spont aneously hypertensive stroke-resistant rats (SHR) and age-matched Wistar-Ky oto rats (WKY) by electron microscopy and immunocytochemistry. Ultrathin se ctions showed no difference in junction structure of cerebral capillaries f rom SHRSP, SHR and WKY, respectively. However, using freeze-fracturing, we observed that the blood-brain barrier specific distribution of tight juncti on particles between P- and E-face in WKY (58.7+/-3.6%, P-face; 41.2+/-5.59 %. E-face) and SHR (53.2+/-19.3%, P-face; 55.6+/-13.25%, E-face) was change d to an 89.4+/-9.9% predominant E-face association in cerebral capillaries from SHRSP. However, the expression of the tight junction molecules ZO-1, o ccludin, claudin-1 and claudin-5 was not changed in capillaries of SHRSP. P ermeability of brain capillaries from SHRSP was not different compared to S HR and WKY using lanthanum nitrate as a tracer. In contrast, analysis of en dothelial cell polarity by distribution of the glucose-1 transporter (Glut- 1) revealed that its abluminal:luminal ratio was reduced from 4:1 in SHR an d WKY to 1:1 in endothelial cells of cerebral capillaries of SHRSP. In summ ary, we demonstrate that early changes exist in cerebral capillaries from a genetic model of hypertension-associated stroke. We suggest that a disturb ed fence function of the tight junctions in SHRSP blood-brain barrier endot helial cells may lead to subtle changes in polarity. These changes may cont ribute to the pathogenesis of stroke. (C) 2000 Elsevier Science B.V. All ri ghts reserved.