1. Comparative effects of N-acetyl-L-cysteine and ramipril on arterial hypertension, insulin resistance, and oxidative stress in chronically glucose-fed rats
- Author
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Midaoui, Adil El, Ismael, Mahmoud Ali, Lu, Huogen, Fantus, I. George, de Champlain, Jacques, and Couture, Rejean
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Antioxidants -- Dosage and administration ,Oxidative stress -- Risk factors -- Control -- Diagnosis -- Care and treatment ,Hypertension -- Risk factors -- Diagnosis -- Care and treatment ,Biological sciences ,Control ,Diagnosis ,Care and treatment ,Risk factors ,Dosage and administration - Abstract
Beneficial effects of an antioxidant (N-acetyl-i,-cysteine, NAC) and an angiotensin 1-converting enzyme (ACE) inhibitor (ramipril) were assessed in a rat model of insulin resistance induced by 10% glucose feeding for 20 weeks. Treatments with NAC (2 g/kg per day) and ramipril (1 mg/kg per day) were initiated at 16 weeks in the drinking fluid. Systolic blood pressure, plasma levels of insulin and glucose, and insulin resistance were significantly higher in rats treated with glucose for 20 weeks. This was associated with a higher production of superoxide anion and NADPH oxidase activity in aorta and liver and with a marked reduction in protein expression of skeletal muscle insulin receptor substrate-1 (IRS-1) in the gastrocnemius muscle. NAC prevented all these alterations. Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta. Ramipril, in contrast to NAC, did not reduce NADPH oxidase activity in aorta and liver or plasma levels of 4-hydroxynonenal and malondialdehyde. Results suggest that the inhibition of the oxidative stress in hypertensive and insulin-resistant states contributes to the therapeutic effects of NAC and ramipril. Whereas NAC exerts effective antioxidant activity in multiple tissues, ramipril appears to preferentially target the vasculature. Key words: ACE inhibitor, hypertension, insulin resistance, N-acetyl-i,-cysteine, oxidative stress, ramipril. On a evalue les effets benefiques d'un antioxydant (N-acetyl-i,-cysteine, NAC) et d'un inhibiteur de l'enzyme de conversion de l'angiotensine-1 (ECA) (Rmpril) dans un modele de rats presentant une resistance a l'insuline induite par l'ingestion de 10 % de glucose pendant 20 semaines. On a incorpore la NAC (2 g/kg par jour) et le ramipril (1 mgikg par jour) durant la 16' semaine dans le liquide de consommation. La pression arterielle systolique, les taux plasmatiques d'insuline et de glucose et la resistance a l'insuline ont ete significativement plus eleves chez les rats traites avec le glucose pendant 20 semaines. Ce resultat a ete associe a une augmentation de la production d'anions superoxyde et de l'activite de la NADPH oxydase dans l'aorte et le foie, et a une reduction marquee de l'expression de la proteine substrat du recepteur de l'insuline (IRS-1) musculaire squelettique dans le muscle gastrocnemien. La NAC a prevenu toutes ces modifications. Bien que le ramipril ait aussi renverse l'hypertension, il a eu un plus faible effet sur la resistance a l'insuline (y compris 1'IRS-1) et a bloque la production d'anions superoxyde dans l'aorte seulement. Le ramipril n'a pas diminue l'activite de la NADPH oxydase dans l'aorte et le foie ou les taux plasmatiques de 4-hydroxynonenal et de malondialdehyde, contrairement a la NAC. Les resultats donnent a penser que l'inhibition du stress oxydatif durant l'hypertension et la resistance a l'insuline contribue aux effets therapeutiques de la NAC et du ramipril. La NAC exerce une activite antioxydante efficace dans de multiples tissus, alors que le ramipril semble davantage cibler le systeme vasculaire. Mots-cles : inhibiteur de PECA, hypertension, resistance a l'insuline, N-acetyl-i,-cysteine, stress oxydatif, ramipril. [Traduit par la Redaction], Introduction The 'metabolic syndrome' is an emerging epidemic worldwide that consists of an association of multiple cardiovascular risk factors (Giugliano et al. 1995). These factors, including hypertension, insulin resistance, and [...]
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- 2008