Abstract-We previously reported increased aortic reactive oxygen species (ROS) production in mineralocorticoid (deoxycorticosterone acetate [DOCA]-salt) hypertensive rats. In the present study, we tested the hypothesis that NADH/NADPH oxidase is responsible for increased ROS production, namely superoxide (O 2 Ϫ ), in aorta from the DOCA-salt rat. Treatment of aortic rings from DOCA-salt rats with the NO synthase inhibitor N-nitro-L-arginine and the xanthine oxidase inhibitor allopurinol did not significantly change O 2 Ϫ production. Furthermore, de-endothelialization of aorta from DOCA-salt rats did not affect O 2 Ϫ production compared with that of sham-operated rats. Thus, xanthine oxidase and uncoupled endothelial NO synthase were not responsible for increased O 2 Ϫ production in the DOCA-salt rats. In contrast, treatment with the NADPH oxidase inhibitor apocynin significantly decreased O 2 Ϫ production in aortic rings from DOCA-salt rats compared with sham-operated rats. Moreover, long-term administration of apocynin (in drinking water, 1.5 mmol/L, 28 days) to DOCA-salt rats significantly decreased systolic blood pressure compared with that of rats treated with DOCA-salt alone. Furthermore, O 2 Ϫ production in aortic rings from DOCA-salt rats treated with apocynin for 28 days was reduced compared with that of untreated DOCA-salt rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that DOCA-salt rats have significantly greater mRNA levels of the NADPH oxidase subunit p22phox than do sham-operated rats. These findings suggest that NADPH oxidase is increased and is responsible for increased O 2 Ϫ production and possibly contributes to increased blood pressure in the DOCA-salt hypertensive rat. Key Words: deoxycorticosterone acetate Ⅲ NADH/NADPH Ⅲ mineralocorticoids Ⅲ hypertension, mineralocorticoid H ypertension, atherosclerosis, and mechanical injury exert common pathological effects on the vessel wall, such as vascular smooth muscle cell (VSMC) proliferation, monocyte/macrophage infiltration, endothelial dysfunction, and increased connective tissue deposition. 1 In addition, these vascular diseases have been shown to be associated with oxidative stress, and there is good evidence implicating angiotensin II in the oxidative stress associated with hypertension. 2,3 However, we 4 and others 5 have reported increased oxidative stress in mineralocorticoid (deoxycorticosterone acetate [DOCA]) hypertension, which is characterized by low angiotensin II levels. We also found that oxidative stress causes increased transcription of genes responsible for the early inflammatory response in the DOCA-salt hypertensive rat. 4 Moreover, a potentially significant consequence of oxidative stress is vascular smooth muscle cell proliferation 6 and NO inactivation, 7 which could play an important role in the vascular changes and causes of hypertension. However, the source of the oxidative (reactive oxygen species [ROS]) stress is not known. Early studies have identified endothelial xanthine oxidase ...

Introduction Hypertension is a risk factor for erectile dysfunction (ED). The pathophysiologic basis of ED in hypertension remains largely unknown. Aim The goal of this study was to test the hypothesis that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity contributes to the development of hypertension-associated ED. Methods Male Sprague-Dawley rats were implanted with osmotic pumps containing saline or angiotensin II (Ang II, 70 ng/min) for 28 days and treated with or without the NADPH oxidase inhibitor apocynin (10 mM) in the drinking water. Main Outcome Measures Erectile function was examined by measuring the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) upon electrical stimulation of the cavernous nerve. Protein expression levels of NADPH oxidase subunits were analyzed by Western blot. Reactive oxygen species production was determined by dihydroethidium (DHE) staining and thiobarbituric acid reactive substances (TBARS) assay. Results Maximum ICP (MaxICP) and ICP area under the curve, which were normalized by MAP, were significantly reduced in Ang II-infused hypertensive rats compared to that of normotensive rats (P <0.05). Protein expression of NADPH oxidase subunit p47phox was significantly increased by 30% in Ang II-infused hypertensive rat penes along with increased DHE staining and TBARS levels (P <0.05) when compared to that of controls. There were no significant changes in p67phox or gp91phox protein expression. Apocynin reduced NADPH oxidase protein expression and TBARS levels as well as improved MaxICP and ICP area under curve in Ang II-infused hypertensive rats (P <0.05). Conclusions These data suggest that activation of NADPH oxidase is a molecular mechanism for hypertension-associated ED. Apocynin treatment exerted protective effects on erectile function through inhibition of NADPH oxidase activity, thereby reducing oxidative stress in Ang II-infused hypertensive rats. This is the first study to identify the importance of NADPH oxidase in the regulation of erectile function in vivo.

Introduction-Thirty million men in the United States suffer from erectile dysfunction (ED) and this number is expected to double by 2025. Considered a major public health problem, which seriously affects the quality of life of patients and their partners, ED becomes increasingly prevalent with age and chronic smoking is a major risk factor in the development of ED.

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