Luteolin restores the renin-angiotensin system to alleviate blood pressure and cardiac changes in secondary hypertensive rats

This study evaluates the effects of luteolin, a natural flavonoid, and its possible mechanisms on hypertension, cardiac dysfunction, and remodeling in rats with secondary hypertension. Renovascular hypertension (RVH) was elicited in male Sprague-Dawley rats using the two-kidney, one-clip technique. Luteolin mitigated hypertension, improved left ventricular (LV) function, and reduced LV remodeling. Alterations in angiotensin-converting enzyme (ACE) activity, angiotensin II, and angiotensin-converting enzyme 2 activity, oxidative stress parameters and antioxidant enzyme activity were normalized by luteolin in RVH animals. Luteolin modulated the expression of angiotensin II type 1 receptor (AT 1 R), Mas receptor (MasR), matrix metalloproteinase-2 (MMP2), and MMP9 in RVH rats. Molecular docking demonstrated a strong affinity between luteolin and ACE. Lisinopril, a positive control, demonstrated effects analogous to those of luteolin. In conclusion, luteolin mitigated hypertension and cardiac alterations by normalizing the renin-angiotensin system and inhibiting oxidative stress. Luteolin mitigated cardiac remodeling through the regulation of the AT 1 R/MasR/MMP2/MMP9 protein expression. • Luteolin alleviates hypertension and cardiac abnormalities. • Luteolin restores classical and non-classical components of the renin-angiotensin system. • Luteolin enhances antioxidant enzyme activity and reduces oxidative stress parameters. • Docking demonstrates a direct interaction between ACE and luteolin, with inhibition.