Effect of treatment with the antioxidant alpha-lipoic (thioctic) acid on heart and kidney microvasculature in spontaneously hypertensive rats

Abstract

Endothelial cells represent an important vascular site of signaling and development of damage during ischemia, inflammation and other pathological conditions. Excessive reactive oxygen species production causes pathological activation of endothelium including exposure of cell to adhesion molecules. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members of the immunoglobulin super-family which are present on the surface of endothelial cells. These molecules represent important markers of endothelial inflammation. The present study was designed to investigate, with immunochemical and immunohistochemical techniques, the effect of treatment with (+/À)-alpha lipoic (thioctic) acid and its enantiomers on heart and kidney endothelium in spontaneously hypertensive rats (SHR). Arterial hypertension is accompanied by an increased oxidative stress status in the heart characterized by thiobarbituric acid reactive substances (TBARS) and nucleic acid oxidation increase. The higher oxidative stress also modifies adhesion molecules expression. In the heart VCAM-1, which was higher than ICAM-1 and PECAM-1, was increased in SHR. ICAM-1, VCAM-1 and PECAM-1 expression was significantly greater in the renal endothelium of SHR. (+/À)-Alpha lipoic acid and (+)-alpha lipoic acid treatment significantly decreased TBARS levels, the nucleic acid oxidation and prevented adhesion molecules expression in cardiac and renal vascular endothelium. These data suggest that endothelial molecules may be used for studying the mechanisms of vascular injury on target organs of hypertension. The effects observed after treatment with (+)-alpha lipoic acid could open new perspectives for countering heart and kidney microvascular injury which represent a common feature in hypertensive end-organs damage.

Cardiovascular Changes Related to Metabolic Syndrome: Evidence in Obese Zucker Rats

“…Indeed, the younger OZRs showed a remarkable increase of PECAM-1, however, the inflammation was reduced and then stabilized at 20 weeks of age, supposing a phenomenon of adaptation over time. The presence of hypertension in the OZRs also accompanied the endothelial dysfunction and the different modulation of the adhesion molecules [56]. There was an age-related increase in oxidative stress, but the inflammatory process seemed independent of age.…”

Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension

“…SHR has a genetic predisposition to develop arterial hypertension, allowing it to study causes, mechanisms, pathology, and behavioral consequences of the disease [27]. Twenty-week-old male SHR (n = 30) and age-matched normotensive Wistar-Kyoto rats (WKY) rats (n = 6) were used and treated, as previously described [20]. Animal manipulation was carried out according to the National and European Community Guidelines for Animal Care (DL 116/92, of application of the European Communities Council Directive, 86/609/EEC) and also following the ethical guidelines of the University of Florence.…”

“…It is due to the presence of an asymmetric carbon in the C3 position. The former enantiomer represents the active form of the compound [20].…”

“…Food intake and body weight were monitored daily, while measurements of systolic blood pressure were performed once a week, in conscious rats, by tail-cuff methods using electronic sphygmomanometer, specific for small animals (Model: GIMA Italy, B3Plus). Animals were anesthetized and then perfused [20]. After, the kidney and heart were dissected out, weighed, fixed for 72 h in 4% paraformaldehyde, dehydrated with alcohol and embedded in paraffin wax.…”

“…Previously, we demonstrated that the antioxidant alpha-lipoic acid (ALA) treatment reduced oxidative stress and prevented adhesion molecule expression in the cardiac and renal vascular endothelium of spontaneously hypertensive rats (SHR) [20]. The SHR is a reliable model of a spontaneously developing pressure load similar to human essential hypertension; thus, it is usually recognized that the SHR represents an analog of essential hypertension in humans [21,22].…”