Asiatic acid alleviates cardiovascular remodelling in rats with L‐NAME‐induced hypertension

Abstract

A previous study demonstrated the antihypertensive effect of asiatic acid. The current study investigates the effect of asiatic acid on cardiovascular remodelling and possible mechanisms involved in Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg per day) for 3 weeks in order to induce hypertension. Hypertensive rats were administered asiatic acid (20 mg/kg per day) or vehicle for a further 2 weeks. It was found that hypertensive rats showed high systolic blood pressure, left ventricular (LV) hypertrophy, increases in LV fibrosis, aortic wall thickness and aortic collagen deposition (P < 0.05). Moreover, decreased plasma nitrate and nitrite (NOx) and increased plasma tumor necrosis factor alpha (TNF-α) were observed in hypertensive rats (P < 0.05). This was consistent with downregulation of endothelial nitric oxide synthase (eNOS) expression and upregulation of inducible nitric oxide synthase (iNOS) expression in heart and aortic tissues (P < 0.05). Levels of malondialdehyde (MDA) in plasma, aortic and heart tissues were significantly increased in hypertensive rats (P < 0.05). Asiatic acid markedly reduced blood pressure, alleviated cardiovascular remodelling, and restored plasma NOx and TNF-α as well as eNOS/iNOS expression in heart and aortic tissues (P < 0.05). Additionally, there was a significant reduction of MDA levels in the tissues of treated hypertensive rats. In conclusion, this study demonstrates the therapeutic effects of asiatic acid on blood pressure and cardiovascular remodelling, which is possibly related to the restoration of eNOS/iNOS expression, and the resulting anti-inflammatory and antioxidant activities.

Acetyl-11-Keto-β-Boswellic Acid Attenuates Prooxidant and Profibrotic Mechanisms Involving Transforming Growth Factor-β1, and Improves Vascular Remodeling in Spontaneously Hypertensive Rats

“…Glycyrrhizin, the similar pentacyclic triterpene compound, has attenuated pulmonary vascular remodeling, as is reported17. Asiatic acid can alleviate cardiovascular remodeling due to its antioxidant effect18, and inhibit cardiac hypertrophy by blocking TGF-β1 pathway19. AKBA has similar structure and activity with Asiatic acid20.…”

“…In another word, drugs inhibiting TGF-β1 pathway or in combination with antioxidant effect may have potential vasoprotection in vascular remodeling. Pentacyclic triterpene compounds structurally similar to AKBA, such as glycyrrhizin and Asiatic acid, have been reported therapeutic effects on cardiovascular remodeling and fibrosis171819. Accordingly, AKBA may also have potential implication in treating vascular remodeling of hypertension, without proper mechanisms, however.…”

Effects of hydrogen sulphide on oxidative stress, inflammatory cytokines, and vascular remodelling in l‐NAME‐induced hypertension

“…Oxidative stress is closely interwoven with vascular inflammation as excessive ROS production creates a pro-inflammatory state and enhances the expression of inflammatory cytokines. 23 Our work showed that aortic IFN-γ and VCAM-1 mRNA were significantly higher in hypertensive rats compared to expression in both the control and H 2 S control groups. Robles-Vera et al 24 found that rats who received l-NAME had higher mRNA levels of IFN-γ, which is Concurrent administration of H 2 S and l-NAME ameliorated the increase in aortic IFN-γ and VCAM-1 mRNA, which is consistent with the observations of Pan et al, 26 who reported that NaHS suppressed (in a concentration-dependent manner) TNF-α-induced expression of ICAM, VCAM-1, E-selectin, and monocyte adhesion in human umbilical vein endothelial cells.…”

“…Oxidative stress is closely interwoven with vascular inflammation as excessive ROS production creates a pro‐inflammatory state and enhances the expression of inflammatory cytokines . Our work showed that aortic IFN‐γ and VCAM‐1 mRNA were significantly higher in hypertensive rats compared to expression in both the control and H 2 S control groups.…”

“…Our work showed that aortic weight, the aortic weight/length ratio, aortic media thickness, and elastin area percentage were significantly increased by l ‐NAME administration in the treated group compared to measurements in the control and H 2 S control groups. These effects may be attributed to increased monocyte and platelet adhesion, which releases growth factors causing increased media thickness . Moreover, the increased elastin area percentage in the hypertensive group could result from increased vascular cell synthetic activity as a result of increased shear stress .…”