Effects of adrenomedullin and its association with doxycycline in the installed hemodynamic disorder induced by acute pulmonary embolism

• Grant number: 12/12291-7
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2013
• End date: January 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• 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

Acute pulmonary embolism (APE) is a major cause of death. We have demonstrated experimentally that infusion of doxycycline, inhibitor of matrix metalloproteinases (MMPs), attenuated pulmonary hypertension induced by APE. It was clinically and experimentally demonstrated that administration of adrenomedullin reduced pulmonary hypertension. Furthermore, it has been suggested that MMPs seems cleave the adrenomedullin into two smaller peptides and, thus eliminating the vasodilatory action of adrenomedullin and forming another vasoconstrictor peptide. However, it is unknown the hemodynamic effects of adrenomedullin infusion during pulmonary hypertension secondary to APE. Therefore, this project will use an animal model of acute pulmonary embolism to investigate (1) the hemodynamic effects of infusion of adrenomedullin after APE. In addition, it will be evaluated (2) the hemodynamic effects of infusion of doxycycline prior to induction of APE and its association with adrenomedullin. The two fundamental hypothesis to be tested in this project are: (1) infusion of adrenomedullin attenuate pulmonary hypertension induced by APE and (2) doxycycline potentiates the effects of adrenomedullin in hemodynamic disorder installed after the EPA. Plasma concentrations of cyclic AMP, cyclic GMP, MMPs, nitrates and nitrites will be determined to evaluate biochemically the hemodynamic effects observed. (AU)