Baicalin mitigates hypertension-linked alterations in the intestinal lymphatic vasculature in part through preserving the functional barrier integrity of lymphatic endothelial cells

Intestinal epithelial barrier impairment serves as an important link between hypertension and systemic inflammation. However, it remains unknown if hypertension is associated with lymphatic alterations in the intestine. Our previous work has demonstrated that baicalin, a naturally occurring anti-inflammatory flavonoid, attenuates intestinal epithelial barrier impairment and inflammation in spontaneously hypertensive rats. The impact of baicalin on hypertension-associated intestinal lymphatic alterations, if present, remains to be inves-tigated too. To address these questions, in vivo and in vitro studies were performed in angiotensin II (ang II)-induced hypertensive mice and ang II-stimulated lymphatic endothelial cells, respectively. The results revealed that ang II infusion led to pronounced dilation of the lacteals and expansion of the lymphatic vascu-lature in the submucosal layer and muscularis externa in the ilium. Meanwhile, the intestinal lymphatics are overtly leaky in the ang II-infused mice. Although losartan, an ang II type 1 receptor blocker, normalized the blood pressure, it failed to mitigate hypertension-linked intestinal lymphatic alterations. However, baicalin treatment protected against intestinal lymphatic alterations, preserved intestinal epithelial barrier integrity and lowered the serum level of Il6 in the ang II-infused mice. Furthermore, baicalin directly antagonized ang II-induced proliferation, migration, decline in the barrier function and disruption of the tight junction integrity in lymphatic endothelial cells. In conclusion, the work here suggests that intestinal lymphatic alterations may serve as a new component of hypertension-linked leaky gut pathologies. Most importantly, baicalin attenuates hypertension-associated intestinal lymphatic alterations in part by directly counteracting ang II-induced func-tional barrier impairment in lymphatic endothelial cells.