Telmisartan improves vascular remodeling through ameliorating prooxidant and profibrotic mechanisms in hypertension via the involvement of transforming growth factor-β1

Abstract

Vascular remodeling is a common complication and pathological basis of hypertension. Transforming growth factor-β1 (TGF-β1)/small mothers against decapentaplegic 3 (Smad3) is considered a potential therapeutic target for vascular remodeling in hypertension. The present study aimed to demonstrate the antifibrotic effects of telmisartan and examined the potential mechanisms associated with its prevention of vascular remodeling. Spontaneously hypertensive rats (SHRs) were treated with telmisartan (20 mg/kg), and vascular contractility, reactivity and oxidative stress were preliminarily evaluated. Vascular pathological alterations and collagen deposition were assessed using hematoxylin and eosin, and Masson staining, respectively. The profibrotic factors, TGF-β1 and Smad3 were evaluated using immunofluorescence and immunohistochemistry. The protein levels of TGF-β1/Smad3, phosphorylated (p-)Smad3, collagen-1 and α-smooth muscle actin in the aorta were assessed using western blot analysis. It was found that telmisartan attenuated chronic vasoconstriction and oxidative stress in the SHRs, and improved vascular reactivity. Telmisartan also restored vascular pathological alterations and decreased collagen deposition. In the vascular wall of the SHRs, telmisartan effectively decreased the protein levels of TGF-β1/Smad3 and p-Smad3. Taken together, these findings indicated that telmisartan, with its antioxidant effect, prevented vascular remodeling in hypertension through preventing the TGF-β1/Smad3 signaling pathway.

Network Pharmacology and In Vivo Analysis of Dahuang-Huangqi Decoction Effectiveness in Alleviating Renal Interstitial Fibrosis

“…Once the PI3K-AKT signaling pathway becomes active, the activation of various other related signaling pathways, which are involved in apoptosis, protein synthesis, metabolism, and cell cycle, can be accelerated [ 28 ]. Consistently, our study supports the assumption that DHHQD could alleviate RIF partly by targeting the PI3K-AKT signaling pathway as well as related signaling pathways, such as the NF- κ B and toll-like receptor signaling pathways [ 29 ].…”

Network Pharmacology and In Vivo Analysis of Dahuang-Huangqi Decoction Effectiveness in Alleviating Renal Interstitial Fibrosis

“…Once the PI3K-AKT signaling pathway becomes active, the activation of various other related signaling pathways, which are involved in apoptosis, protein synthesis, metabolism, and cell cycle, can be accelerated [ 28 ]. Consistently, our study supports the assumption that DHHQD could alleviate RIF partly by targeting the PI3K-AKT signaling pathway as well as related signaling pathways, such as the NF- κ B and toll-like receptor signaling pathways [ 29 ].…”

Telmisartan inhibits the non-canonical TGF-β/JAK2/STAT3 signaling pathway and prevents carbon tetrachloride-induced liver fibrosis in rats

“…Our data is in line with the evident antioxidant activity seen in telmisartan treated group. These data are also in accordance with other reports in which telmisartan has been shown to significantly reduce lipid peroxidation, inflammatory cytokine secretion and expression, henceforth reduces the progression of tissue injury 26,28,35,36 . Telmisartan has been also documented to significantly reduce inflammatory cell infiltration in liver tissue 26,37 .…”

“…These data are in accordance with the increase in serum hepatic injury markers (ALT and AST) that can be explained by the elevated oxidative stress and the consequent lipid peroxidation and liver injury that may alter transport and permeability function of cellular membrane in injured hepatic cells, resulting in outflow of the enzymes from hepatic cells into the blood flow 25 . Conversely telmisartan treatment showed antioxidant and hepatoprotective effects as evidenced from the elevated TAC, decreased liver index, MDA, and serum liver injury markers in CCl4 intoxicated animals 26,28 . The hepatoprotective effects of telmisartan may be in part based on drug's antioxidative action 29,30 .…”

Investigation of the effects of tadalafil and telmisartan in bleomycin-induced pulmonary fibrosis on rats

“…The role of reactive oxygen species and angiotensin on this process is well studied. Thus, angiotensin receptor blocked by telmisartan, is thought to be a potential target for preventing fibrosis in lungs [24]. Our histopathological findings were parallel to the hypothesis.…”

Network Pharmacology and In Vivo Analysis of Dahuang-Huangqi Decoction Effectiveness in Alleviating Renal Interstitial Fibrosis

“…Once the PI3K-AKT signaling pathway becomes active, the activation of various other related signaling pathways, which are involved in apoptosis, protein synthesis, metabolism, and cell cycle, can be accelerated [ 28 ]. Consistently, our study supports the assumption that DHHQD could alleviate RIF partly by targeting the PI3K-AKT signaling pathway as well as related signaling pathways, such as the NF- κ B and toll-like receptor signaling pathways [ 29 ].…”

Telmisartan inhibits the non-canonical TGF-β/JAK2/STAT3 signaling pathway and prevents carbon tetrachloride-induced liver fibrosis in rats

“…Our data is in line with the evident antioxidant activity seen in telmisartan treated group. These data are also in accordance with other reports in which telmisartan has been shown to significantly reduce lipid peroxidation, inflammatory cytokine secretion and expression, henceforth reduces the progression of tissue injury 26,28,35,36 . Telmisartan has been also documented to significantly reduce inflammatory cell infiltration in liver tissue 26,37 .…”

“…These data are in accordance with the increase in serum hepatic injury markers (ALT and AST) that can be explained by the elevated oxidative stress and the consequent lipid peroxidation and liver injury that may alter transport and permeability function of cellular membrane in injured hepatic cells, resulting in outflow of the enzymes from hepatic cells into the blood flow 25 . Conversely telmisartan treatment showed antioxidant and hepatoprotective effects as evidenced from the elevated TAC, decreased liver index, MDA, and serum liver injury markers in CCl4 intoxicated animals 26,28 . The hepatoprotective effects of telmisartan may be in part based on drug's antioxidative action 29,30 .…”

Investigation of the effects of tadalafil and telmisartan in bleomycin-induced pulmonary fibrosis on rats

“…The role of reactive oxygen species and angiotensin on this process is well studied. Thus, angiotensin receptor blocked by telmisartan, is thought to be a potential target for preventing fibrosis in lungs [24]. Our histopathological findings were parallel to the hypothesis.…”

Network Pharmacology and In Vivo Analysis of Dahuang-Huangqi Decoction Effectiveness in Alleviating Renal Interstitial Fibrosis

“…Once the PI3K-AKT signaling pathway becomes active, the activation of various other related signaling pathways, which are involved in apoptosis, protein synthesis, metabolism, and cell cycle, can be accelerated [ 28 ]. Consistently, our study supports the assumption that DHHQD could alleviate RIF partly by targeting the PI3K-AKT signaling pathway as well as related signaling pathways, such as the NF- κ B and toll-like receptor signaling pathways [ 29 ].…”

Telmisartan inhibits the non-canonical TGF-β/JAK2/STAT3 signaling pathway and prevents carbon tetrachloride-induced liver fibrosis in rats

“…Our data is in line with the evident antioxidant activity seen in telmisartan treated group. These data are also in accordance with other reports in which telmisartan has been shown to significantly reduce lipid peroxidation, inflammatory cytokine secretion and expression, henceforth reduces the progression of tissue injury 26,28,35,36 . Telmisartan has been also documented to significantly reduce inflammatory cell infiltration in liver tissue 26,37 .…”

“…These data are in accordance with the increase in serum hepatic injury markers (ALT and AST) that can be explained by the elevated oxidative stress and the consequent lipid peroxidation and liver injury that may alter transport and permeability function of cellular membrane in injured hepatic cells, resulting in outflow of the enzymes from hepatic cells into the blood flow 25 . Conversely telmisartan treatment showed antioxidant and hepatoprotective effects as evidenced from the elevated TAC, decreased liver index, MDA, and serum liver injury markers in CCl4 intoxicated animals 26,28 . The hepatoprotective effects of telmisartan may be in part based on drug's antioxidative action 29,30 .…”

Investigation of the effects of tadalafil and telmisartan in bleomycin-induced pulmonary fibrosis on rats

“…The role of reactive oxygen species and angiotensin on this process is well studied. Thus, angiotensin receptor blocked by telmisartan, is thought to be a potential target for preventing fibrosis in lungs [24]. Our histopathological findings were parallel to the hypothesis.…”