Hyperuricaemia-Induced Hypertension in Rats by Regulating the RhoA/ROCK Pathway.

INTRODUCTION

Hyperuricaemia (HUA) is associated with hypertension, but the mechanisms remain unclear. This study investigated whether the RhoA/ROCK pathway mediates HUA-induced vascular remodelling and hypertension.

METHODS

Thirty male Sprague-Dawley rats were divided into control, HUA, and fasudil (ROCK inhibitor) groups. Serum uric acid, creatinine, and blood pressure were measured biweekly. Histopathology, qPCR, and Western blotting assessed thoracic aortic changes and RhoA/ROCK pathway activation. Rat vascular smooth muscle cells (VSMCs) were treated with uric acid, with or without RhoA/ROCK inhibitors, to evaluate nitric oxide (NO) levels and protein expression.

RESULTS

HUA significantly increased systolic blood pressure, aortic media thickness, smooth muscle cell proliferation, and expression of RhoA, ROCK 1/2, and MLC1, with elevated phosphorylation of MLC and MYPT-1. Fasudil reduced blood pressure and ameliorated vascular remodelling but did not lower uric acid levels. In VSMCs, HUA decreased NO content, enhanced RhoA membrane translocation, and increased ROCK 2 expression, effects reversed by RhoA or ROCK inhibitors.

CONCLUSION

HUA promotes hypertension by activating the RhoA/ROCK pathway, leading to vascular remodelling and dysfunction. Inhibition of this pathway attenuates HUA-induced hypertension, highlighting the mechanistic relevance of the RhoA/ROCK pathway.