Effects of melatonin on the passive mechanical response of arteries in chronic hypoxic newborn lambs

Abstract

Chronic hypoxia is a condition that increases the cardiovascular complications of newborns gestated and born athigh altitude (HA), over 2500 m above sea level (masl). A particularly complex pathology is pulmonary arterialhypertension of the neonate (PHN), which is increased at HA due to hypobaric hypoxia. Basic and clinicalresearch have recognized that new treatments are needed, because current ones are, in general, palliative andwith low effectiveness. Therefore, recently we have proposed melatonin as a potential adjuvant treatment toimprove cardiopulmonary function. However, melatonin effects on the mechanical response of the arteries andtheir microstructure are not known. This study assesses the effects of a neonatal treatment with daily low doses ofmelatonin on the passive biomechanical behavior of the aorta artery and main pulmonary artery of PHN lambsborn in chronic hypobaric hypoxia (at 3600 masl). With this purpose, ex-vivo measurements were made on axialstretch, tensile and opening ring tests together with a histological analysis to explore the morphometry andmicrostructure of the arteries. Our results show that the passive mechanical properties of the aorta artery andmain pulmonary artery of lambs do not seem to be affected by a treatment based on low melatonin doses.However, we found evidence that melatonin has microstructural effects, particularly, diminishing cell proliferation,which is an indicator of antiremodeling capacity. Therefore, the use of melatonin as an adjuvant againstpathologies like PHN would present antiproliferative effect at the microstructural level, keeping the macroscopicproperties of the aorta artery and main pulmonary artery.