title: Low-level lead exposure changes endothelial modulation in rat resistance pulmonary arteries.
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 (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.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil.
authors.forename: Emilia Polaco
authors.initials: EP
authors.lastname: Covre
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil.
authors.forename: David Domingues
authors.initials: DD
authors.lastname: Freire
authors.affiliation: Department of Chemistry, Federal University of Espirito Santo, Vitoria, Brazil.
authors.forename: Bruna Miurim
authors.initials: BM
authors.lastname: Dalfior
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil.
authors.forename: Vinícius Bermond
authors.initials: VB
authors.lastname: Marques
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil.
authors.forename: Rogério Faustino
authors.initials: RF
authors.lastname: Ribeiro
authors.affiliation: Department of Chemistry, Federal University of Espirito Santo, Vitoria, Brazil.
authors.forename: Maria Tereza Weitzel Dias
authors.initials: MTWD
authors.lastname: Carneiro Lima
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil. Electronic address: leodossantos@hotmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Dos Santos
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009942:Organometallic Compounds; D013481:Superoxides; D009569:Nitric Oxide; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; C008261:lead acetate
keywords: Heavy metal; Mulvany; Pulmonary artery; Vascular reactivity