Low-level lead exposure changes endothelial modulation in rat resistance pulmonary arteries |
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| Affiliation: | 1. Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil;2. Department of Chemistry, Federal University of Espirito Santo, Vitoria, Brazil;1. The First Hospital of Jilin University, Changchun, 130021, China;2. KCHRI at the Department of Pediatrics, School of Medicine, University of Louisville, Louisville, 40202, USA;3. Chinese–American Research Institute for Diabetic Complications, Wenzhou Medical College School of Pharmacy, Wenzhou, 325035, China;4. Department of Bioinformatics and Biostatistics, School of Public Health and Information Sciences, University of Louisville, Louisville, KY 40202, USA;5. Department of Pathology, Inner Mongolia Forestry General Hospital, Yakeshi, 022150, China;6. Department of Medicine, School of Medicine, University of Louisville, Louisville, 40202, USA;1. Scientific and Technological pole, INRCA, Ancona, Italy;2. Department of Molecular and Clinical Sciences, Histology, Polytechnic University of Marche Region, Ancona, Italy |
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| Abstract: | Lead exposure induces hypertension and endothelial dysfunction. However, the effects on the pulmonary vasculature have not been explored. In this study, rats exposed to lead acetate for seven days (4 μg/100 g on the 1st day and 0.05 μg/100 g/day i.m. subsequently) had lead blood level of 3.9 ± 0.7 μg/dL and increased right ventricular pressures. There was an increased Pb deposition and superoxide anions production in the pulmonary arteries, associated with reduced vasoconstriction but unchanged endothelium-dependent vasodilatation to acetylcholine (ACh). In both groups, inhibition of the nitric oxide (NO) synthase with L-NAME blocked the response to ACh, while indomethacin (cycloxygenase inhibitor) had no effect. Incubation with nonspecific potassium channel blocker (tetraethylammonium) reduced the ACh-induced vasodilatation only in the Pb group. Apamin (SKCa channel blocker) and 4-aminopyridine (Kv channel blocker), but not iberiotoxin (BKCa channel blocker), also inhibited this response in the Pb group. The vasodilatation to exogenous NO was reduced by Pb, while relaxation to the cGMP analogue was similar between groups. Concordantly, the protein level of soluble guanylate cyclase (sGC) was reduced. In conclusion, short-term and low-level exposure to Pb changes pulmonary haemodynamic and increases oxidative stress. The pulmonary vasculature exhibited increased hyperpolarization by the Kv and SKCa channels, probably as a compensatory mechanism to the decreased responsiveness to NO. |
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