Sub-chronic lead exposure produces β1-adrenoceptor downregulation decreasing arterial pressure reactivity in rats

Life Sci. 2017 Jul 1:180:93-101. doi: 10.1016/j.lfs.2017.05.009. Epub 2017 May 9.

Abstract

Lead is considered a causative factor for hypertension and other cardiovascular diseases.

Aims: To investigate the effects of sub-chronic lead exposure on blood pressure reactivity and cardiac β1-adrenoceptor activity and to evaluate whether the effects found in vitro are similar to those found in vivo.

Main methods: Male Wistar rats were randomly distributed into two groups: control rats (Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days.

Key findings: Blood pressure in the Pb rats increased starting from the first week of treatment until the end of the study [systolic blood pressure, Ct: 122±4 vs. Pb: 143±3mmHg; diastolic blood pressure, Ct: 63±4 vs. Pb: 84±4mmHg]. The heart rate was also increased (Ct: 299±11 vs. Pb: 365±11bpm), but the pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats. Isoproterenol increased the left ventricular systolic and end-diastolic pressure, and heart rate only in Ct rats, suggesting that lead induced β1-adrenoceptor downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb rats, suggesting the involvement of cyclooxygenase-derived products (which are associated with reduced nitric oxide bioavailability) in this process.

Significance: These findings offer further evidence that the effects of sub-chronic lead exposure in vitro can be reproduced in vivo-even at low concentrations-thus triggering mechanisms for the development of hypertension. Therefore, lead should be considered an environmental risk factor for cardiovascular disease.

Keywords: Blood pressure; Pressure reactivity; Sub-chronic lead exposure; Sympathetic hyperactivity; β-adrenoceptor.

MeSH terms

  • Animals
  • Arterial Pressure / drug effects*
  • Cardiovascular Diseases / chemically induced
  • Down-Regulation
  • Heart Rate / drug effects
  • Hexamethonium / pharmacology
  • Hypertension / chemically induced*
  • Indomethacin / pharmacology
  • Isoproterenol / pharmacology
  • Lead / administration & dosage
  • Lead / toxicity*
  • Losartan / pharmacology
  • Male
  • Nitric Oxide / metabolism
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-1 / genetics*
  • Risk Factors

Substances

  • Receptors, Adrenergic, beta-1
  • Phenylephrine
  • Lead
  • Nitric Oxide
  • Hexamethonium
  • Losartan
  • Isoproterenol
  • Indomethacin