Hemodynamic effects of doxycycline combined with adrenomedullin during acute pulmonary embolism- induced pulmonary hypertension

Matrix metalloproteinases (MMPs) may limit severely the pulmonary vasodilatory and inotropic effects of adrenomedullin during pulmonary hypertension. While doxycycline inhibits MMPs and prevents the hemodynamic disorders associated with acute pulmonary embolism (APE), no previous study evaluated if doxycycline enhances adrenomedullin-induced pulmonary vasodilation and contributes to the attenuation of APE-induced pulmonary hypertension. Hemodynamic and respiratory changes were determined in animals not subjected to any intervention (Sham group), or animals subjected to APE induced by microspheres treated with saline (PE group) or 10 mg/kg of doxycycline (Dox+PE group) 30 min before APE or 50 ng/kg/min of adrenomedullin (PE+Adm group) 30 after APE, or doxycycline combined with adrenomedullin (Dox+PE+Adm group). Doxycycline produced no effect on significant temporal decreases in pulmonary vascular resistance index and increases in cardiac index (both by 25%) observed with adrenomedullin. Adrenomedullin produced moderate systemic hypotension. Significant decreases in arterial oxygen partial pressure were observed after doxycycline or APE, but these changes were not affected by adrenomedullin. These results show that the combined administration of doxycycline and adrenomedullin is not advantageous compared with adrenomedullin alone, thus suggesting that adrenomedullin counteracted the pulmonary vasoconstriction and it may help in the therapy of the detrimental acute hemodynamic consequences of APE. Correspondence to: Carlos A. Dias-Junior, Pharm D, PhD, Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University, Distrito de Rubiao Junior, S/N, 18.618-970 Botucatu, SP, Brazil; E-mail: [email protected]