Effect of chronic hypoxia on contents of urotensin II and its functional receptors in rat myocardium.

Abstract

The cyclic peptide urotensin II (UII) has recently been cloned in mammals and reported to constrict rat pulmonary arteries potently. An enhanced maximal response was shown in rats exposed to chronic hypoxia. The aim of this study was to investigate changes in plasma and myocardial UII levels and its receptor sites in crude sarcolemma of ventricles from chronic hypoxic rats. We observed that rats exposed to chronic hypoxia for 4 weeks developed pulmonary hypertension and right ventricular hypertrophy. Compared with controls, the UII content in hypoxic rats was increased by 97.5% (45.24 +/- 7.1 vs. 22.9 +/- 3.24pg/mg protein, P < 0.01) in the right ventricle and 33.2% (24.89 +/- 0.99 vs. 18.68 +/- 2.04pg/mg protein, P < 0.01) in the left ventricle, respectively. However, there was no significant difference in plasma (27.44 +/- 3.11 vs. 27.82 +/- 5.57pg/ml, P > 0.05) and lung tissue levels (34.03 +/- 4.63 vs. 33.74 +/- 4.06 pg/ mg protein, P > 0.05) between the control and hypoxic groups. The time course of the binding of [125I]UII to crude ventricular sarcolemma was specific and time dependent. Scatchard plot analysis of the data demonstrated that the maximal number of specific binding sites (Bmax) in both the right and left ventricles was upregulated in the hypoxic group. Moreover, Bmax in the right ventricular specimens was upregulated to a greater extent than in the left ventricle (increased by 114% and 25% in the right and left ventricles, respectively, compared with control group, P < 0.01). In contrast, the UII binding affinity in right and left ventricular membranes from hypoxic rats was decreased (the dissociation constant Kd) increased by 20% and 33%, respectively compared with controls, P < 0.01). These results indicate that UII may act as an autocrine and/or paracrine hormone rather than as a circulating hormone, playing important roles in the development of ventricular hypertrophy induced by chronic hypoxia, and that the pathophysiological significance of UII in pulmonary and cardiovascular alteration induced by chronic hypoxia deserves further investigation.