Cyclooxygenase-2 Inhibitors Attenuate Angiotensin II–Induced Oxidative Stress, Hypertension, and Cardiac Hypertrophy in Rats

Abstract

Abstract-Angiotensin II is an important oxidative stress mediator. Our previous studies have indicated that the potent antioxidative properties of acetylsalicylic acid play an important role in its cardiovascular protective effects. There are some ongoing controversies concerning the use of selective cyclooxygenase-2 inhibitors in cardiovascular disease. The aim of this study was to determine whether the cyclooxygenase-2 selective inhibitors rofecoxib and nimesulide possess antioxidative and cardiovascular protective effects against angiotensin II. Chronic subcutaneous angiotensin II infusion increased cardiovascular but not colonic tissue superoxide production, heart/body weight ratio, and blood pressure. Moreover, angiotensin II selectively increased cardiac cyclooxygenase-2 but not cyclooxygenase-1 expression, which was totally prevented by acetylsalicylic acid treatment. Similar to acetylsalicylic acid, rofecoxib or nimesulide treatments significantly attenuated angiotensin II-induced oxidative stress, hypertension, and cardiac NAD(P)H oxidase subunit p47 phox expression. Rofecoxib also reduced cardiac hypertrophy. Treatment with nonselective anti-inflammatory drugs ibuprofen, indomethacin, or salicylic acid did not show any effect on angiotensin II-induced superoxide production, hypertension, or cardiac hypertrophy. Although acetylsalicylic acid and salicylic acid inhibited angiotensin II-induced nuclear factor B (NF-B) activation, nimesulide did not modify NF-B activation. In conclusion, cyclooxygenase-2 pathway is implicated in angiotensin II-induced oxidative stress and deleterious cardiovascular changes. Rofecoxib and nimesulide produced significant antioxidative effect by reducing NAD(P)H oxidase-dependent superoxide generation. These effects seem to be independent of NF-B inhibition.

Recurrent insulin-induced hypoglycemia induces AngII and COX2 leading to renal (pro)renin receptor expression and oxidative stress

“…A previous report showed that COX2 plays a significant role in AngIIinduced NADPH oxidase-derived O2-production (Wu et al 2005). Rofecoxib (Selective COX2 inhibitors) blocked superoxide formation and reduced cardiac hypertrophy, which provided antioxidative properties during enhanced AngII activity (Wu et al 2005). …”

Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats

“…Furthermore, a high prevalence of diseases, such as hypertension, diabetes, atherosclerosis, osteoarthritis and cancer, in elderly patients promotes an increased use of NSAIDs [14] . Reports on the effect of NSAIDs on the cardiovascular system are controversial [15][16][17][18] . NSAIDs cause increased blood pressure by blocking the synthesis of prostaglandins that regulate vascular tone and sodium excretion [19,20] .…”

Efeitos Da Angiotensina Ii No Sistema Cardiovascular

“…Desta forma, a via cicloxigenase-2 parece também participar do estresse oxidativo e dos efeitos deletérios ao sistema cardiovascular (Wu et al, 2005).…”

“…Observações oriundas, principalmente, de modelos experimentais, têm estimulado pesquisas visando o potencial terapêutico dos anti-oxidantes, como o ácido caféico, antiiflamatórios e mais enfaticamente os medicamentos anti -TNF-α (Li et al, 2000;Li et al, 2005;Wu et al, 2005).…”