Carotid atherosclerosis in elderly hypertensive patients: potential role of endothelin and plasma antioxidant capacity

Abstract

Endothelin-1 (ET-1) and oxidative stress are involved in the development of hypertension-induced cardiovascular complications. The aim of this study was to evaluate the relationship between plasma ET-1 level and plasma antioxidant capacity and carotid atherosclerosis. In 61 treated patients with hypertension (44 women, 35 diabetics, mean age 72.4 ± 7.2 years) medical histories, ambulatory blood pressure, blood tests (glucose, creatinine, cholesterol, haemoglobin A1c (HbA1c), ET-1) and common carotid artery intima-media thickness (CCA-IMT) measurement were carried out. Plasma antioxidant capacity was assessed by the ferric-reducing ability of plasma (FRAP). Subjects with diabetes presented with higher concentrations of glucose (7.01 ± 2.3 vs 5.14±0.6 mmol l À1 , Po0.001), HbA1c (7.75±2.1 vs 6.1±1.2%, Po0.001) and ET-1 (1.36±0.53 vs 1.01± 0.4 pg ml À1 , Po0.01), and lower cholesterol level (5.02±0.8 vs 5.86±1.3 mmol l À1 , Po0.01). A significant positive correlation between CCA-IMT and ET-1 plasma concentration (r ¼ 0.40, Po0.001) and reverse relationship between CCA-IMT and FRAP (r ¼ À0.36, Po0.01) was observed. In a stepwise regression analysis, after adjustment for all confounders, CCA-IMT was independently influenced by age, systolic blood pressure (SBP), HbA1c and ET-1. When FRAP was included in the regression model, CCA-IMT was significantly influenced by age, FRAP, HbA1c and SBP. ET-1 promotes the increase in CCA-IMT contributing to the development of end-organ damage. Plasma antioxidant capacity may modulate this deleterious effect, but whether better antioxidant defence may prevent against the development of atherosclerosis remains to be elucidated.

Endothelin-1 but not angiotensin II contributes to functional aging in murine carotid arteries

“…Pharmacologic inhibition of the renin angiotensin-system has been proven effective in the prevention of stroke and dementia in hypertensive patients [1]. Moreover, observational studies have shown that carotid artery intima-media thickness (IMT) positively correlates with plasma ET-1 concentrations in hypertensive [49, 50] and in diabetic [51] patients, and that carotid artery IMT is positively associated with plasma ET-1 levels in young women with polycystic ovary syndrome [52]. Supporting the findings of the present study, the relationship between plasma ET-1 concentration and carotid artery IMT also appears to be dependent on plasma antioxidant capacity [50], suggesting that the deleterious vascular effects of ET-1 are partly ROS-mediated.…”

“…Moreover, observational studies have shown that carotid artery intima-media thickness (IMT) positively correlates with plasma ET-1 concentrations in hypertensive [49, 50] and in diabetic [51] patients, and that carotid artery IMT is positively associated with plasma ET-1 levels in young women with polycystic ovary syndrome [52]. Supporting the findings of the present study, the relationship between plasma ET-1 concentration and carotid artery IMT also appears to be dependent on plasma antioxidant capacity [50], suggesting that the deleterious vascular effects of ET-1 are partly ROS-mediated. Whether interfering with the vascular activity of ET-1 can prevent age-induced carotid artery disease and the increased risk for stroke and cognitive impairment associated with it awaits future studies.…”

The effects of aging on the functional and structural properties of the rat basilar artery

“…Therefore, plasma antioxidant capacity can potentially affect the oxidative stress in the peripheral tissues. Moreover, it was previously reported that carotid atherosclerosis was associated with the reduced serum antioxidant capacity (Skalska and Grodzicki ). Accordingly in this study, decreased plasma antioxidant capacity may be an indicator of increased oxidative stress in the basilar artery, the latter which leads to structural and functional impairment.…”

Insights into ETA subtype selectivity of benzodiazepine endothelin receptor antagonists by 3D-QSAR approaches

“…Extensive preclinical and clinical studies, mainly with ET A receptor antagonists, have shown excellent therapeutic benefits in disease such as pulmonary hypertension [9], heart failure [10], atherosclerosis [11], systemic hypertension [12], chronic renal failure [13] and solid tumors [14]. These results indicate endothelin receptor antagonists, especially those selective for the ET A receptor subtype, may constitute a novel and potentially important class of agents for the treatment of the aforementioned pathological conditions.…”