Published Online
on October 17, 2005

A more recent version of this article appeared on December 1, 2005

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Submitted on July 13, 2005
Revised on July 28, 2005

Increased Aortic NADPH Oxidase Activity in Rats With Genetically High Angiotensin-Converting Enzyme Levels

Jorge E. Jalil^*; Alfonso Pérez; María Paz Ocaranza; Jorge Bargetto; Alfonso Galaz; and Sergio Lavandero

From the Department of Cardiovascular Diseases, Medical School, P. Universidad Católica de Chile (J.E.J., M.P.O., A.P., J.B., A.G.), and Departamento de Bioquímica and Biología Molecular, Facultad Ciencias Químicas y Farmacéuticas (J.B., A.G., I.G., S.L.), ICBM, Facultad de Medicina (S.L.) and Centro FONDAP Estudios Moleculares de la Célula (S.L.), Universidad de Chile, Santiago.

^* To whom correspondence should be addressed. E-mail: jjalil{at}med.puc.cl.

Abstract--In humans and rats, angiotensin I-converting enzyme activity is significantly determined by a gene polymorphism. Homozygous Brown Norway rats have higher plasma angiotensin I-converting enzyme activity and circulating angiotensin II (Ang II) levels than Lewis rats. Because Ang II induces NAD(P)H oxidase activation, we hypothesized here that Brown Norway rats have higher vascular NAD(P)H oxidase activity and superoxide anion production than Lewis rats. Homozygous Brown Norway (n=15) and Lewis (n=13) male rats were used. Plasma angiotensin I-converting enzyme activity (by fluorimetry), Ang II levels (by high-performance liquid chromatography and radioimmunoassay), and aortic NAD(P)H oxidase activity, as well as superoxide anion production (by chemiluminescence with lucigenin) were measured. Plasma angiotensin I-converting enzyme activity and Ang II levels were 100% higher in Brown Norway rats than in Lewis rats (P<0.05). Aortic angiotensin I- converting enzyme, but not Ang II, was elevated (P<0.05). Aortic superoxide anion production and NAD(P)H oxidase activity were 300% and 260% higher in Brown Norway than in Lewis rats, respectively (P<0.05), which was not observed in Brown Norway rats treated with candesartan (10 mg/kg per day for 7 days). Endothelial NO synthase activity in the aorta from Brown Norway rats was significantly lower than in Lewis rats. However, inducible NO synthase activity and both endothelial NO synthase and inducible NO synthase mRNA and protein levels were similar in both genotypes. In summary, Brown Norway rats have higher vascular NAD(P)H oxidase activity and superoxide anion production than Lewis rats, suggesting the presence of a higher level of vascular oxidative stress in rats with genetically higher angiotensin I-converting enzyme levels. This effect is mediated through the angiotensin I receptor.

Key words: angiotensin-converting enzyme • polymorphism • nitric oxide

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