Effects of doxycycline in hypertension induced by lead exposure: quantification of vasoactive peptides

• Grant number: 12/21305-1
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2013
• End date: February 28, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Carlos Alan Candido Dias Junior
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Lead is a metal very versatile for numerous industrial activities and this promote their wide distribution. Almost everyone have lead in their bodies as a result of exposure to exogenous sources. Several experimental and clinical studies have showed lead-induced hypertension. Lead may directly activates the matrix metalloproteinases (MMP's) and recent findings suggest that the matrix metalloproteinase type-2 (MMP-2) may play a role in the early stages of lead-induced hypertension as well as other models of hypertension. Doxycycline (an inhibitor of MMP's) attenuated both increased levels of MMP-2 and the elevation of blood pressure induced by lead and these effects were also observed in hypertensive situations not related to lead exposure. However, the mechanisms that explain how increased MMP-2 activity correlates with hypertension remain unclear. It seems that MMP-2 can enhance vascular contractility by cleaves peptides involved in the control of vascular tone, promoting the degradation of vasodilators peptides (such as the calcitonin gene related peptide - CGRP, or adrenomedullin) or cleavage of big endothelin-1 in endothelin-1 (a vasoconstrictor peptide). However, it is still unknown the effect of doxycycline on plasma levels of vasoactive peptides after hypertension induced by exposure to lead. Therefore, this present project proposes the use of an animal model of hypertension induced by exposure to lead to investigate (1) the pressure effects of doxycycline on the lead-induced hypertension and (2) if there are changes in plasma levels of CGRP, adrenomedullin or endothelin-1 after lead-induced hypertension, as well as (3) whether doxycycline inhibits these effects. (AU)