The effect of telmisartan, an angiotensin receptor blocker, on alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens

Tezcan, Kutluhan; Yananlı, Hasan Raci; Demirkapu, Mahluga Jafarova; Gören, M. Zafer; Sakalli, Halil Eren; Colombo, Giancarlo; Aker, Rezzan

doi:10.1016/j.alcohol.2021.08.004

Cited by 5 publications

(2 citation statements)

References 65 publications

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“…After alcohol enters the body, it is mainly metabolized by the liver, and 10%–15% can be metabolized by the kidneys. And, the metabolites of alcohol such as acetaldehyde and butyric acid can also stimulate the body's unbalanced regulation of aldosterone and angiotensin [ 12 ], increase kidney load, gradually change the structure of kidney tissue, and further aggravate the damage of kidney function.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Effect of Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats Based on TIMP-1/MMP-24 Pathway

Song

Yuan

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Objective. To establish a rat model of alcoholic kidney injury and detect the expression of TIMP-1/MMP-24 in the kidneys of rats with alcoholic kidney injury at the molecular pathological level, so as to explore the mechanism of alcohol abuse leading to kidney injury and renal interstitial fibrosis as well as the alleviation of alcohol-induced kidney injury and inhibition of renal interstitial fibrosis by dapagliflozin. Methods. 48 male rats were randomly divided into 4 groups: control group, alcohol group, alcohol + dapagliflozin group, and alcohol + losartan group, each with 12 rats. Different drugs were administered by gavage for modeling and treatment. Six days later, the rats were sacrificed, blood was collected from the heart to separate the serum, and the blood creatinine (Scr) and urea nitrogen (BUN) contents were detected biochemically. After blood collection, the kidney tissue was taken and fixed in10% neutral formalin. The expression of renal tissue inflammatory factors (CRP, IL-6, and TNF-α) and renal fibrosis indexes (LN, HA, and TGF-β1) were detected; MMP-24 and TIMP-1 in the kidney tissue of rats in different treatment groups were detected, and Smad3 expression was also detected. Results. After treatment, the general condition of the alcohol + dapagliflozin group and the alcohol + losartan group improved to different degrees. The weight first decreased and then gradually increased over time. There was no statistical difference in the weight change between the two groups; Compared with the control group, the Scr level, BUN content, renal index, inflammatory factors, and renal fibrosis indexes in the alcohol group were significantly increased ( P < 0.05 ); after 6 weeks of treatment, in the alcohol + dapagliflozin group and alcohol + losartan group, Scr level, BUN content, kidney index, inflammatory factors, and renal fibrosis indexes were significantly decreased ( P < 0.05 ); the expression of MMP-24 in the kidney tissue of the control group was upregulated, and the expression of TIMP-1 and Smad3 was downregulated; MMP-24 expression was downregulated, and TIMP-1 and Smad3 expression was significantly upregulated ( P < 0.05 ) in the rats of the alcohol group. After dapagliflozin and losartan treatment, MMP-24 expression gradually increased and TIMP-1 and Smad3 expression gradually decreased ( P < 0.05 ). Conclusion. Long-term large-scale alcohol intake can cause kidney tissue damage and fibrotic lesions. The expression of fibrotic cytokines such as TIMP-1 and Smad3 will increase, and the expression of MMP-24 will be decreased. However, dapagliflozin and losartan have certain therapeutic effects on the abovementioned lesions. The mechanism may be downregulating TIMP-1 and Smad3 and upregulating the expression of MMP-24 and other cytokines in the kidney.

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Section: Discussionmentioning

confidence: 99%

Exploring the Effect of Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats Based on TIMP-1/MMP-24 Pathway

Song

Yuan

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…The ARB candesartan has been shown to reduce morphine-induced inflammatory response and cellular activation in murine-derived microglial cells [ 59 ], significantly decrease methamphetamine self-administration and seeking behavior in male Sprague–Dawley rats [ 60 ] and pretreatment with candesartan in Wistar rats has been shown to attenuate the development of amphetamine-induced behavior sensitization [ 61 , 62 ]. Moreover, acute intracerebroventricular administration of telmisartan, but not losartan, reduces alcohol consumption in Sardinian alcohol-preferring rats [ 63 ] and treatment with valsartan has been observed to prevent morphine-tolerance in Wistar rats [ 64 ]. The discrepancies observed between ARBs and their potential to be used in addiction may be due to their ability (e.g., azilsartan, candesartan, telmisartan and valsartan) or inability (e.g., eprosartan, irbesartan, losartan and olmesartan) to penetrate the BBB [ 37 , 65 ].…”

Section: Introductionmentioning

confidence: 99%

Structural Features Influencing the Bioactive Conformation of Angiotensin II and Angiotensin A: Relationship between Receptor Desensitization, Addiction, and the Blood–Brain Barrier

Moore,

Ridway,

Gadanec

et al. 2024

IJMS

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The N-terminal portion of the octapeptide angiotensin II (DRVYIHPF; AngII), a vasopressor peptide that favorably binds to, and activates, AngII type 1 receptor (AT1R), has an important role in maintaining bioactive conformation. It involves all three charged groups, namely (i) the N-terminal amino group cation, (ii) the Asp sidechain anion and (iii) the Arg guanidino cation. Neutralization of any one of these three charged groups results in a substantial reduction (<5%) in bioactivity, implicating a specialized function for this cluster. In contrast, angiotensin A (ARVYIHPF; AngA) has reduced bioactivity at AT1R; however, replacement of Asp in AngII with sarcosine (N-methyl-glycine) not only restores bioactivity but increases the activity of agonist, antagonist, and inverse agonist analogues. A bend produced at the N-terminus by the introduction of the secondary amino acid sarcosine is thought to realign the functional groups that chaperone the C-terminal portion of AngII, allowing transfer of the negative charge originating at the C-terminus to be transferred to the Tyr hydroxyl-forming tyrosinate anion, which is required to activate the receptor and desensitizes the receptor (tachyphylaxis). Peptide (sarilesin) and nonpeptide (sartans) moieties, which are long-acting inverse agonists, appear to desensitize the receptor by a mechanism analogous to tachyphylaxis. Sartans/bisartans were found to bind to alpha adrenergic receptors resulting in structure-dependent desensitization or resensitization. These considerations have provided information on the mechanisms of receptor desensitization/tolerance and insights into possible avenues for treating addiction. In this regard sartans, which appear to cross the blood–brain barrier more readily than bisartans, are the preferred drug candidates.

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Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System

Gallardo-Ortíz,

Oros-González,

Rodríguez-Manzo

et al. 2024

Psychopharmacology

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The effect of telmisartan, an angiotensin receptor blocker, on alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens

Cited by 5 publications

References 65 publications

Exploring the Effect of Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats Based on TIMP-1/MMP-24 Pathway

Exploring the Effect of Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats Based on TIMP-1/MMP-24 Pathway

Structural Features Influencing the Bioactive Conformation of Angiotensin II and Angiotensin A: Relationship between Receptor Desensitization, Addiction, and the Blood–Brain Barrier

Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System

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