Browsing by Author "Bargetto, J"

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    Effect of hypertension on angiotensin-(1-7) levels in rats with different angiotensin-I converting enzyme polymorphism
    (PERGAMON-ELSEVIER SCIENCE LTD, 2006) Ocaranza, MP; Palomera, C; Roman, M; Bargetto, J; Lavandero, S; Jalil, JE
    To determine circulating angiotensin-(1-7) [Ang-(1,7)] levels in rats with different angiotensin converting enzyme (ACE) genotypes and to evaluate the effect of hypertension on levels of this heptapeptide, plasma levels of angiotensin II (Ang II) and Ang-(1-7) were determined by HPLC and radioimmunoassay in (a) normotensive F-0 and F-2 homozygous Brown Norway (BN; with high ACE) or Lewis (with low ACE) rats and (b) in hypertensive F-2 homozygous male rats (Goldblatt model). Genotypes were characterized by PCR and plasma ACE activity measured by fluorimetry. Plasma ACE activity was 2-fold higher (p < 0.05) in homozygous BN compared to homozygous Lewis groups. In the Goldblatt groups, a similar degree of hypertension and left ventricular hypertrophy was observed in rats with both genotypes. Plasma Ang II levels were between 300-400% higher (p < 0.05) in the BN than in the Lewis rats, without increment in the hypertensive animals. Plasma Ang-(1-7) levels were 75-87% lower in the BN rats (p < 0.05) and they were significantly higher(p < 0.05) in the hypertensive rats from both genotypes. Plasma levels of Ang II and Ang-(1-7) levels were inversely correlated in the normotensive rats (r = -0.64; p < 0.001), but not in the hypertensive animals. We conclude that there is an inverse relationship between circulating levels of Ang II and Ang-(1-7) in rats determined by the ACE gene polymorphism. This inverse relation is due to genetically determined higher ACE activity. Besides, plasma levels of Ang-(1-7) increase in renovascular hypertension. (c) 2005 Elsevier Inc. All rights reserved.
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    Increased aortic NADPH oxidase activity in rats with genetically high angiotensin-converting enzyme levels
    (LIPPINCOTT WILLIAMS & WILKINS, 2005) Jalil, JE; Perez, A; Ocaranza, MP; Bargetto, J; Galaz, A; Lavandero, S
    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.