title: Combination therapy for the cardiovascular effects of perinatal lead exposure in young and adult rats.
abstract: BACKGROUND
  Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes.
  
  
  OBJECTIVE
  To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated).
  
  
  RESULTS
  Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05).
  
  
  CONCLUSIONS
  All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.
authors: Departamento de Farmacologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP, Brazil.
authors: Andréia Fresneda
authors: AF
authors: Gaspar
authors: Departamento de Farmacologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP, Brazil.
authors: Sandra
authors: S
authors: Cordellini
mesh_terms: D000367:Age Factors; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001120:Arginine / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002319:Cardiovascular System / Q000187:drug effects; D002614:Chelating Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007774:Lactation / Q000187:drug effects; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000150:complications / Q000188:drug therapy*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000188:drug therapy; D017208:Rats, Wistar; D004113:Succimer; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D002614:Chelating Agents; D007854:Lead; D004656:Enalapril; D001120:Arginine; D004113:Succimer