[PP.16.13] 42-DAY CHRONIC EXPOSURE TO ALUMINUM CHLORIDE PROMOTES VASCULAR DYSFUNCTION AND INCREASES BLOOD PRESSURE IN RATS

    loading  Checking for direct PDF access through Ovid

Abstract

Objective:

To investigate the effects of chronic exposure of aluminum chloride (AlCl3) on blood pressure, vascular reactivity and oxidative stress.

Design and method:

20 three-month-old male Wistar rats were divided into two groups and treated orally for 42 days: a) Control - ultrapure water; b) AlCl3 - at a dose of 100 mg/kg bw (Basic & Clin Pharm & Toxicol 105: 98–104, 2009). Systolic blood pressure (SBP) was measured using tail-cuff plethysmography. Vascular function was studied in aorta by isometric tension recording and in mesenteric resistance arteries (MRA) using a small-vessel dual chamber myograph. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were performed. Vasoconstrictor response to phenylephrine (PHE) in presence and absence of endothelium and in presence of NOS inhibitor (L-NAME), potassium channels blocker (TEA), NAD(P)H oxidase inhibitor (apocynin), superoxide dismutase, non-selective COX inhibitor (indomethacin), selective COX-2 inhibitor (NS 398), and AT1 selective receptor blocker (losartan), were analyzed. Systemic and vascular reactive oxygen species (ROS), lipid peroxidation and antioxidant capacity, were measured. Results were expressed as mean and SEM, compared by t–test or ANOVA followed by Bonferroni (P < 0,05). Ethical Approval 028/2014.

Results:

AlCl3 exposure increased SBP (Ct: 118, 4 ± 1,17 vs Al: 130,2 ± 1,83* mmHg), decreased ACh induced concentration-dependent relaxation, increased vasoconstrictor response to PHE (MRA - Rmax % to KCl Ct: 110,4 ± 8,8 vs Al: 123,1 ± 0,8 %*, Aorta - Ct: 105,8 ± 7,9 vs Al: 124,2 ± 23 %*), decreased the endothelium vasoconstrictor – modulation, nitric oxide (NO) bioavailability, potassium channels involvement, as well as increased ROS production from NAD(P)H oxidase and contractile prostanoids mainly from COX-2. Aluminum also increased the angiotensin pathway vascular modulation to PHE. Vascular and plasmatic ROS production, lipid peroxidation as well as antioxidant capacity increased after Al exposure.

Conclusions:

Our results point to the excess of ROS mainly from NAD(P)H oxidase after aluminum exposure and the increased vascular prostanoids from COX-2 acting in concert to decrease NO bioavailability, thus inducing vascular dysfunction and increased blood pressure. Therefore, the most significant environmental contaminant appears to poses a risk for cardiovascular system.

Related Topics

    loading  Loading Related Articles