title: Serum vasoactive agents in lead-treated rats.
abstract: BACKGROUND
  It is still unknown whether mechanisms of the hypertensinogenic effect of lead include changes in synthesis or release of vasoactive agents. This question is essential with regard to lead dissemination in the human environment as well as to frequent occurrence of arterial hypertension.
  
  
  OBJECTIVE
  The aim of the study was to evaluate the effect of chronic exposure to lead on the vasoactive agents in blood in relation to redox system activity in vessel walls and to disturbances in homeostasis of essential metals. Using lead in double small, hypertensive doses we tried to estimate whether this effect dependents on the degree of lead exposure.
  
  
  METHODS
  The study was performed on the male Buffalo rats which were given lead in drinking water, 50 or 100 ppm (lead acetate dissolved in distillate water) for 12 weeks. Control rats were given distillate water. Rats were fasted starting the night before the experiment, and the next day were anesthetized intramuscularly with ketaminum at a dose of 300 mg/kg body weight. The abdomen was opened and the aorta was isolated. Blood samples were drawn from heart, abdominal and thoracic aorta and then kidneys were excised. Serum nitric oxide and prostaglandin PGF(2alpha) concentrations were measured using R&D systems, and the plasma endothelin-1 level with enzymoimmunoassay; 5% homogenates of aorta were prepared from thoracic fragment in saccharose buffer. Lipid peroxides in homogenates were determined colorimetrically and glutathione was measured using colorimetric assay BIOXYTECH GSH-400. The concentration of metals (lead, copper and zinc) in blood and aorta were determined with a plasma spectrometer.
  
  
  RESULTS
  The study shows different changes in toxicological and biochemical status, depending on the dose of metal. Mean serum nitric oxide concentration was higher in rats treated with lead in a dose of 50 ppm (p < 0.01) or 100 ppm (p < 0.001) than in the control group. The plasma endothelin-1 level was lower in rats given lead in a dose of 50 ppm (p < 0.05) than in controls, whereas serum prostaglandin PGF(2alpha) concentration was similar in all animals. Glutathione concentration in aorta was higher in both groups of rats treated with lead (p < 0.001) in comparison to controls. There were positive linear dependencies between: (a) blood lead and serum nitric oxide; (b) aorta glutathione and serum nitric oxide; (c) copper in aorta and glutathione in aorta; (d) serum zinc and plasma endothelin-1 concentrations.
  
  
  CONCLUSIONS
  It was concluded, that lead in small doses increases synthesis and/or releases nitric oxide and its concentration in serum. This effect of lead is probably connected with the augmented production of glutathione in vessel walls. Additionally, lead in a dose of 50 ppm provokes the decrease in the level of plasma endothelin-1, probably through the decreased level of serum zinc. We suppose that the mechanisms responsible for the vascular effect of lead differ even within the range of hypertensive doses.
authors.affiliation: Department of Internal Medicine, Occupational Diseases and Hypertension, Wrocław Medical University, Poland. annaskoc@ak.am.wroc.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Skoczyńska
authors.forename: Ewa
authors.initials: E
authors.lastname: Stojek
authors.forename: Helena
authors.initials: H
authors.lastname: Górecka
authors.forename: Anna
authors.initials: A
authors.lastname: Wojakowska
mesh_terms: D000818:Animals; D003300:Copper / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D007854:Lead / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D007855:Lead Poisoning / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF; D014665:Vasodilator Agents / Q000378:metabolism / Q000633:toxicity*; D015032:Zinc / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D014665:Vasodilator Agents; D007854:Lead; D009569:Nitric Oxide; D003300:Copper; D015237:Dinoprost; D015032:Zinc