Abstract
Hypertension is a major risk factors for stroke, cardiovascular diseases, and chronic kidney diseases. Although taking antihypertension drugs improves the prognosis of hypertensive patients to a certain extent, there are still lots of refractory hypertension and non-adherent patients. Therefore, it is imperative to explore more effective and targeted treatment approaches. Herein, we construct a multifunctional photothermal hydrogel to treat hypertension and cardiac remodeling through renal denervation (RDN) under 808 nm near-infrared (NIR) laser irradiation. The prepared multifunctional hydrogel, which is customized based on renal perivascular microenvironment, exhibits excellent stretchability, mechanical properties, flexibility and adhesion, ensuring it with remarkable conformability to the dynamic movements of the renal arteries throughout RDN procedures. Photothermal RDN achieved significant blood pressure reduction, with sustained decreases of 13.3 ± 2.5 mmHg in systolic blood pressure and 10.6 ± 1.2 mmHg in diastolic blood pressure, persisting for 8 weeks post-treatment. Additionally, a reduction in myocardial fibrosis and cardiomyocyte hypertrophy is observed, which indicative of the alleviation of cardiac remodeling. The antihypertensive effect of photothermal RDN is mediated through inhibition of the renin-angiotensin-aldosterone system (RAAS) pathway and activation of the cGMP-PKG signaling cascade. The photothermal hydrogel-mediated RDN treatment provides a promising and innovative strategy for treating hypertension and cardiac remodeling.