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It is known that the endothelin and angiotensin receptors ETA/ETB and AT1 on smooth muscle cells induce contraction and stimulate proliferation and cell hypertrophy. In hypertensive animals and in situations of altered blood flow, e.g. in stroke, there is an up-regulation of ET- and AT-receptors due to de novo transcription. In order to simulate this situation we hypothesized that changes in perfusion pressure may result in altered expression of protein encoding for the receptors ETA, ETB, AT1, and AT2 in the rat basilar artery.
Segments of the rat basilar artery (n = 6) were cannulated with glass micropipettes, pressurized and luminally perfused in a perfusion chamber. After exposure to normal (80/70 mm Hg) or high (140/130 mm Hg) pressure at constant flow for 16 hours the vessel segments were immersed in a fixative solution, dehydrated, frozen, cut in a cryostat and immunohistology-stained for ET- and AT-receptor protein.
ETB- and AT1-receptor proteins were significantly up-regulated after high perfusion pressure compared to normal perfusion pressure at 16 hours (p < 0.05). Immunohistochemistry showed that the up-regulated proteins were located mainly in the smooth muscle cells in the arterial wall.
The results from our rat perfusion model show significant up-regulation of ETB- and AT1-receptor proteins after high perfusion pressure. Since the increased protein expression was located in the smooth muscle layer, the results of our study have suggested a shift in the role of the endothelin and angiotensin system towards a worsening of the pathophysiology in the early stages of hypertension.
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