Puerarin Improves Vascular Insulin Resistance and Cardiovascular Remodeling in Salt-Sensitive Hypertension

Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks. An additional group of DS rats was pretreated with puerarin and NS for 10 days, then switched to HS plus puerarin for five weeks. HS for five weeks increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and aortic hypertrophy with increased the expression of phosphor-ERK1/2 in the aorta and heart; puerarin attenuated cardiac and aortic hypertrophy, cardiac fibrosis and phosphor-ERK1/2 with a mild reduction in SBP. Hypertensive rats also manifested impairment of acetylcholine- and insulin-mediated vasorelaxation and insulin-mediated Akt and eNOS phosphorylation associated with the activation of NF[Formula: see text]B/TNF[Formula: see text]/JNK pathway. Puerarin improved acetylcholine- and insulin-mediated vasorelaxation and insulin-stimulated Akt/NO signaling with the inhibition of the NF[Formula: see text]B inflammatory pathway. Our results demonstrated that in salt-sensitive hypertension, puerarin improved vascular insulin action with cardiovascular beneficial effects. Our results found that the underlying mechanisms may involve its inhibition of NF[Formula: see text]B/JNK and ERK1/2 pathway. These results suggest that puerarin could be used as a new antihypertensive agent to expand our armamentarium for the prevention and treatment of end-organ damage in individuals with hypertension and metabolic diseases.