Renal transplantation increases angiotensin II receptor-mediated vascular contractility associated with changes of epigenetic mechanisms.

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Hypertension is one of the most common complications following renal transplantation, and it increases the risk of graft loss and other cardiovascular diseases. Previous studies have revealed that the use of angiotensinII (AngII) blockers for preventing and treating hypertension is closely associated with higher survival following renal transplantation. However, the cellular and molecular mechanisms by which the vascular contractility of the recipient is altered in response to AngII following renal transplantation have not been fully elucidated. In the present study, using the Fisher‑Lewis rat kidney transplantation model, the blood pressure(BP) of the conscious transplant recipient was measured following the intravenous administration of AngII. In addition, the mechanisms underlying the AngII-mediated vascular contractility via the type1 and type2AngII receptors (AT1R and AT2R, respectively) in large and small-resistance blood vessels were determined in the recipient after renal transplantation. The results showed that renal transplantation significantly increased the AngII-stimulated BP of the rats. Additionally, exvivo contractility experiments using aorta and mesenteric arteries revealed that the contractions induced by AngII were significantly strengthened in the recipient following renal transplantation, and were associated with an increased intracellular Ca2+ concentration. Losartan almost eradicated the AngII-induced contractions whereas PD-123319 had no apparent effects on the AngII-induced contractions in the aorta and mesenteric arteries of the recipient. Furthermore, the expression levels of AT1R but not AT2R were significantly increased in the vasculature of the recipient following renal transplantation, which exhibited a close association with selective DNA demethylation detected in the promoter region of the vascular AT1aR gene. These results indicate that changes of recipient vascular AT1R gene expression, occurring through a mechanism involving DNA methylation, increase the vascular contractility in response to AngII. This may lead to the increased risk of hypertension following renal transplantation.