Quercetin attenuates the progression of monocrotaline-induced pulmonary hypertension in rats

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature. Quercetin is a natural flavonoid and has a variety of pharmacological effects including improvement of endothelial cell function. However, its pharmacological effects on pulmonary hypertension have been rarely reported. We sought to observe the protective effect of quercetin in rats with monocrotaline induced PAH. We divided 30 male Sprague-Dawley rats randomly into three groups with ten rats in each group: the monocrotaline group, the quercetin group and the control group. We found that, compared with the controls, the mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index in the monocrotaline group were significantly higher (P < 0.01). Quercetin caused a significant reduction both in the mPAP and right ventricular hypertrophy index compared with the monocrotaline group (P < 0.01) while no difference was found between the quercetin group and the control group (P > 0.05). Monocrotaline induced a marked increase in the wall thickness (WT) in small and mid-sized pulmonary arteries compared with the controls (P < 0.01). Monocrotaline also induced a marked increase in the wall area (WA) in small [(56.38±6.65)% in monocrotaline vs. (19.80±4.63)% in control] and mid-sized [(43.71±5.38)% in monocrotaline vs. (14.24±3.66)% in control] pulmonary arteries (P < 0.01). Quercetin treatment markedly reduced monocrotaline induced increase in both WT and WA (P < 0.01), which, however, still remained significantly elevated compared with those of the controls (P < 0.01). Furthermore, compared with controls, proliferating cell nuclear antigen (PCNA) expression in the pulmonary artery tissues was markedly increased by monocrotaline [(45.59±1.27) in monocrotaline vs. (9.64±0.69) in controls], which was significantly attenuated by quercetin. Our animal experiment indicated that quercetin could have protective effects on monocrotaline-induced PAH.

Keywords: PCNA; monocrotaline; pulmonary arterial hypertension; quercetin.

Fig. 1. Hematoxylin-eosin staining of the pulmonary artery in the control group (A), rats treated with monocrotaline (B), or with monocrotaline and quercetin (C).

The wall in monocrotaline treated rats was thicker than that in controls, which was attenuated by quercetin. Long arrow indicates vessel lumen and short arrow indicates vessel wall. (×400)

Fig. 2. Immunohistochemistry of the pulmonary artery.

Tissue sections of the pulmonary artery from rats in the control group (A), the monocrotaline group (B) and the quercetin group (C) were immunohistochemically stained with anti-PCNA antibodies. Long arrow indicates vessel lumen and short arrow indicates vessel wall. (×400)