Browsing by Author "Jalil, JE"

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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.
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    Perindopril regulates beta-agonist-induced cardiac apoptosis
    (LIPPINCOTT WILLIAMS & WILKINS, 2005) Galvez, AS; Fiedler, JL; Ocaranza, MP; Jalil, JE; Lavandero, S; Diaz Araya, G
    Administration of the P-adrenergic agonist isoproterenol results in cardiac apoptosis. The effect of short-term P-adrenergic stimulation by isoproterenol on the activity of plasma, lung, and left ventricular (LV) angiotensin 1-converting enzyme (ACE) activity and its association with the development of cardiac apoptosis was investigated. P-Adrenergic stimulation for 24 hours produced an early increase only in the proapoptotic proteins bax and bcl-XS without changes in the levels of the antiapoptotic protein bcl-XL. The ratio between these bcl family proteins was indicative of apoptosis and correlated with an early and significant increase (300%) in DNA laddering. However, after 5 days of the P-adrenergic stimulation, the ratio changed in favor of antiapoptotic proteins and correlated with the absence of DNA fragmentation. In addition, LV and plasma ACE activities increased markedly with isoproterenol over the study period up to 5 days. ACE activity also regulated expression of the antiapoptotic gene bcl-XL. The administration of perindopril (an ACE inhibitor) prevented the observed increase in bax and bcl-XS levels and attenuated (50% decrease, P < 0.05) the effect of isoproterenol on DNA fragmentation. Thus, early and transient cardiac apoptosis triggered by the beta-adrenergic agonist isoproterenol is reversed in the presence of perindopril.
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    Prevalence of the angiotensin I converting enzyme insertion deletion polymorphism, plasma angiotensin converting enzyme activity, and left ventricular mass in a normotensive Chilean population
    (ELSEVIER SCIENCE INC, 1999) Jalil, JE; Piddo, AM; Cordova, S; Chamorro, G; Braun, S; Jalil, R; Vega, J; Jadue'P, L; Lavandero, S; Lastra, P
    The aim of this study was to estimate the prevalence of the different alleles of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and associated plasma ACE activity, as well as cardiac echocardiographic structure, in a healthy Chilean population. We selected 117 healthy normotensive subjects (aged 45 to 60 years, middle socioeconomic status, nonobese, and nondiabetic) from a population-based study concerning the prevalence of risk factors for chronic diseases (Conjunto de Acciones Para la Reduccion Multifactorial de las Enfermedades no Transmisibles [CARMEN]),