Low-level lead exposure changes endothelial modulation in rat resistance pulmonary arteries
| Autor: | Rogério Faustino Ribeiro, Leonardo dos Santos, Maria Tereza Weitzel Dias Carneiro Lima, David D. Freire, Emilia Polaco Covre, Bruna Miurim Dalfior, Vinicius Bermond Marques |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Physiology Vasodilation Pulmonary Artery Pharmacology Nitric Oxide Apamin Nitric oxide 03 medical and health sciences chemistry.chemical_compound Soluble Guanylyl Cyclase Superoxides Organometallic Compounds medicine Animals Channel blocker Rats Wistar Cyclic GMP Tetraethylammonium business.industry Potassium channel blocker Iberiotoxin Acetylcholine Rats Oxidative Stress 030104 developmental biology chemistry Vasoconstriction Molecular Medicine Endothelium Vascular medicine.symptom business medicine.drug |
| Zdroj: | Vascular Pharmacology. 85:21-28 |
| ISSN: | 1537-1891 |
| Popis: | 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 (4μg/100g on the 1st day and 0.05μg/100g/day i.m. subsequently) had lead blood level of 3.9±0.7μg/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. |
| Databáze: | OpenAIRE |
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