Flow-induced vascular remodeling in the mesenteric artery of spontaneously hypertensive rats

Abstract

The effect of an increased blood flow on vascular remodeling was studied in the mesenteric arteries of 11–12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar–Kyoto rats (WKY). Increased blood flow was induced by selective ligation of mesenteric arteries. Nearby arteries with normal blood flow were used as controls. 7–10 days after the ligation procedure, mesenteric arteries were fixed in situ at maximal relaxation by perfusion fixation. Morphometric measurement of vascular dimension was carried out with confocal microscopy. Apoptotic cells were detected by the TdT-mediated dUTP nick-end labelling method. Cell growth was quantified by using proliferating cell nuclear antigen (PCNA) in sections of paraffin-embedded vessels. In SHR, elevated blood flow increased the vessel wall dimension and the number of smooth muscle cell (SMC) layers and also increased the wall-to-lumen ratio and the number of PCNA-positive SMC, but did not change lumen size or number of apoptotic SMC. In WKY, on the other hand, increased blood flow resulted in an increase in lumen diameter, a reduction of apoptotic SMC, but no change in wall-to-lumen ratio, number of SMC layers, or number of PCNA-positive SMC. These results showed that mesenteric arteries from hypertensive and normotensive rats respond to an increase in blood flow differently: a lumen enlargement with reduced SMC apoptosis in WKY, but an increased wall-to-lumen ratio with enhanced SMC growth in SHR. Although it remains to be determined whether flow alteration is one of the initiating factors in the development of vascular remodeling in hypertension, we speculate that an increase in cardiac output, and therefore an increase in shear stress that occurs in young SHR, contributes to vascular remodelling in this model of hypertension.