Dynamic Aspects of Regulatory Lung Peptides in Chronic Hypoxic Pulmonary Hypertension

Abstract

Male Sprague-Dawley rats were placed in hypobaric hypoxia for 17–21 d (FlO₂ 10%) to establish pulmonary hypertension (PH) and control rats were kept in normo-baric room air. Right mean atrial and ventricular pressures (PRA, PRV) were recorded, left ventricular (LV) blood was collected, and lungs were perfused with heparinized saline. Hearts were removed to evaluate right ventricular (RV) hypertrophy (RV/(IV + septum)%). Peptides were quantitated with radioimmunoassay in lung tissue extracts and plasma. Wet lung weight, PRA, PRV, and RV/(LV + S)% were higher and body weight was lower in hypoxia rats, and lung morphometry revealed increased arterial medial thickness (MT/OD%) and elastification of arterioles and capillaries. Lung tissue CGRP, PYX γ₂-MSH, and SOM were higher in PH rats and ANP was unchanged. Blood AVP, CGRP, PYY, VIP, and SOM were reduced in PH rats and ANP was unchanged. Lung levels of PYY and SOM correlated significantly with the time in hypoxia and with all parameters examined and CGRP and γ₂-MSH correlated with all but medial thickness. PYY had the highest correlation of the peptides with body weight, PRV, and RV/(LV + S)%, and SOM the highest with time in hypoxia, wet lung weight, PRA, MT/OD%, and elastification of arterioles and capillaries. Blood peptides correlated inversely with these parameters. ANP had the overall weakest correlations and CGRP, PYY, and SOM had the highest. SOM correlated the highest with arterial medial hypertrophy, PRV, RV hypertrophy, and elastification of peripheral capillaries. VIP correlated the highest of the blood peptides with body weight and wet lung weight. Statistically significant correlations do not necessarily imply causal relationships. The putative roles of these peptides in pulmonary function are discussed.