ABSTRACT
OBJECTIVES: To investigate the role of angiotensin inhibition on lipid peroxidation (LPO) and renal pathology in ischemic reperfusion (IR). MATERIAL AND METHOD: Male Wistar rats were subjected to 15-, 30-, 45- or 60- minutes ofrenal ischemia (I) by left renal artery occlusion. In the 30-minute I group, reperfusion (R) for I day (13,R) was performed in additional animals that had been treated with water, angiotensin converting enzyme inhibitor (ACE]; enalapril 5 mg/kg/d), or angiotensin receptor type 1 blocker (ARB; losartan 10 mg/kg/d) one day before I and were continued for 1 day after R. Renal tissue malondialdehyde (MDA), an indicator of LPO, was examined during I and IR periods. Renal pathology was also determined. RESULTS: During ischemia, renal tissue MDA levels were increased throughout the 60-minute ischemic period and was maximum at 30 minutes of ischemia (p < 0.01). Histological changes in 30-minutes I group showed slight tubular cell congestion and mild interstitial edema. One day after reperfusion, MDA levels were still elevated (p < 0. 01) when compared with sham. Progression of renal pathology was observed after I day of reperfusion. Both ACEI and ARB could attenuate the heightened MDA levels (p < 0.01). IR-induced renal injury was markedly diminished by administration ofACEI as well as by ARB. CONCLUSION: These results indicate that inhibition of angiotensin could reduce lipid peroxidation and ameliorate renal injury during IR condition.
Subject(s)
Angiotensin I/antagonists & inhibitors , Animals , Kidney/blood supply , Lipid Peroxidation/drug effects , Male , Rats , Rats, Wistar , Reperfusion Injury/prevention & controlABSTRACT
Angiotensin-(1-7) (Ang-(1-7)) is now considered to be a biologically active member of the renin-angiotensin system. The functions of Ang-(1-7) are often opposite to those attributed to the main effector component of the renin-angiotensin system, Ang II. Chronic administration of angiotensin-converting enzyme inhibitors (ACEI) increases 10- to 25-fold the plasma levels of this peptide, suggesting that part of the beneficial effects of ACEI could be mediated by Ang-(1-7). Ang-(1-7) can be formed from Ang II or directly from Ang I. Other enzymatic pathways for Ang-(1-7) generation have been recently described involving the novel ACE homologue ACE2. This enzyme can form Ang-(1-7) from Ang II or less efficiently by the hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation. The biological relevance of Ang-(1-7) has been recently reinforced by the identification of its receptor, the G-protein-coupled receptor Mas. Heart and blood vessels are important targets for the formation and actions of Ang-(1-7). In this review we will discuss recent findings concerning the biological role of Ang-(1-7) in the heart and blood vessels, taking into account aspects related to its formation and effects on these tissues. In addition, we will discuss the potential of Ang-(1-7) and its receptor as a target for the development of new cardiovascular drugs.
Subject(s)
Animals , Humans , Angiotensin I/physiology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Peptide Fragments/physiology , Angiotensin I/antagonists & inhibitors , Angiotensin I/biosynthesis , Blood Pressure/drug effects , Cardiovascular Physiological Phenomena/drug effects , Coronary Vessels/drug effects , Endothelial Cells , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/biosynthesis , Renin-Angiotensin System/physiologyABSTRACT
Se realizó un estudio sobre la síntesis de renina y las modificaciones en el número de células que se produce durante la inhibición crónica de la enzima convertidora de la Ang II en ratones. Veinte ratones CF1, hembras de 15 días de edad, inmediatamente después del destete, recibieron 20 mg/l de maleato de enalapril (ME) con el agua de beber durante 18 meses y se compararon con un grupo control. El tejido renal fue procesado y estudiado con técnicas inmunohistoquímicas con microscopía óptica y electrónica utilizando un anticuerpo policlonal antirrenina y se realizó hibridización in situ para rasteo de ARNm de renina con una sonda marcada con diagoxigenina. Los parámetros calculados fueron el número de aparatos yuxtaglomerulares (MAYG), de arteriolas aferentes (AA) y vasos arcuatos (VA) inmunomarcados con antirrenina y con antidigoxigenina. Con microscopía electrónica se determinó el número de partículas de oro por gránulo de renina. Se demostró aumento del número de células productoras de renina en los animales que recibieron crónicamente ME, más allá del AYG y de la AA ya que se observó marcación en vasos arcuatos. La media de porcentagem MAYG y porcentagemMAA fue menor en los animales controles (Con) que en los tratados (TRA). No se marcaron los VA en el grupo Con, y sí en los animales Tra. La distribución del ARN fue diferente en los animales con inhibición del SRA que en los controles. Los signos de hibridización fueron significativamente menores en los animales Con, tanto el porcentagemSAYG, el porcentagemSAA. En los VA sólo se observaron signos en los animales tratados porcentagem SVA. La cantidad de partículas de oro en las células productoras de renina fue diferente entre los dos grupos de animales. La media del número de partículas de oro en los gránulos de renina perteneciente al AYG de los animales Con. fue significativamente menor que en los tratados. En este trabajo se demostró que los animales que tienen inhibido crónicamente la producción de Ang II por ME, aumentan la síntesis, el número y la localización de células productoras de renina en la vasculatura renal, recapitulando situaciones que ocurren durante el desarrollo embriológico de mamíferos y en vertebrados primitivos adultos