What is the clinical evidence from this study?

Study design: Other. Population: Hypertension (animal model). Intervention: Male sex vs. Female sex. Primary outcome: Hydroethidine oxidation (superoxide anion production) (p=<0.05).

December 4, 2003Open Access

Gender differences in superoxide generation in microvessels of hypertensive rats: role of NAD(P)H-oxidase

Q: What are the key findings of this study?

Male hypertensive rats exhibited markedly increased superoxide anion production compared to females (30.9% vs 12.3%; p<0.05), driven by AT-1-dependent overexpression of NAD(P)H-oxidase components.

Key Result

Male hypertensive rats exhibited markedly increased superoxide anion production compared to females (30.9% vs 12.3%; p<0.05), driven by AT-1-dependent overexpression of NAD(P)H-oxidase components.

Structured PICO

Population

Male and female spontaneously hypertensive rats (SHR) evaluated for gender differences in superoxide generation.

Exposure

Treatment with DPI (NAD(P)H-oxidase inhibitor) or losartan (Angiotensin-II type 1 receptor antagonist)

Comparator

Male vs. female SHR; untreated controls

Outcome

Nitric oxide (NO) generation and superoxide anion (O2-) production in mesenteric arteriolessurrogate

Male spontaneously hypertensive rats exhibit higher basal superoxide anion concentration than females due to AT-1-dependent overexpression of NAD(P)H-oxidase components, suggesting a mechanism for gender differences in cardiovascular disease.

Main Result

Absolute Event Rate: 30.9% vs 12.3%

p-value: p=<0.05

Abstract

OBJECTIVE: This study is aimed to explore whether gender plays a role in the generation of nitric oxide (NO) and superoxide anion (O(2)(-)) in microvessels of hypertensive rats (SHR), as well as the potential mechanisms involved in these effects. METHODS AND RESULTS: NO generation in mesenteric arterioles was evaluated by measuring NO synthase (NOS) activity and protein expression. Oxidative stress was studied in vivo in mesenteric arterioles from male and female SHR by hydroethidine microfluorography. Although we did not observe any sex-related differences in NO generation, we found that hydroethitine oxidation is markedly increased (30.9+/-2.4%) in male compared to female (12.3+/-2.5%; p<0.05), demonstrating a gender difference in O(2)(-) production. The treatment of mesenteries with DPI (NAD(P)H-oxidase inhibitor) and treatment of SHR with losartan Angiotensin-II type 1 (AT-1) receptor antagonist markedly reduced O(2)(-) production in male, while produced a minor effect in female, suggesting that overexpression/activity of AT-1 receptor and NAD(P)H-oxidase contribute for the sexual dimorphism in superoxide generation. Immunoblot analyses provide evidences of overexpression of the NAD(P)H-oxidase components p22(phox), gp91(phox), p47(phox) and p67(phox) in arterioles from male in comparison to female. Losartan treatment inhibited the overexpression of these subunits in male, without affecting the responses in female. CONCLUSION: Taken together, our findings demonstrate that male SHR presents higher superoxide anion concentration under basal condition than does female. An AT-1-dependent overexpression of the NAD(P)H-oxidase components may account for the sexual dimorphism in oxidative stress, and may play an important role in the noted gender differences on incidence of cardiovascular disease.