ENHANCED ENDOTHELIN-1 AND ENDOTHELIN RECEPTOR GENE-EXPRESSION IN CHRONIC HYPOXIA

To test the hypothesis that endothelin (ET)-1 synthesis and ET recepto r levels are increased selectively in the lung of rats with chronic hy poxic pulmonary hypertension, the current study examined the effects o f exposure to chronic hypoxia (10% O-2, 1 atm, 4 wk) on pulmonary arte rial pressure, ET-1 levels in plasma and lung, and ET-1 and ET(A) and ET(B) receptor mRNA levels in lung, heart, pulmonary artery, aorta, ki dney, spleen, and liver. Hypoxic exposure was associated with increase s in pulmonary arterial pressure, plasma ET-1 levels, ET-1 mRNA in lun g and pulmonary artery, and ET-1 stores and ET(A) and ET(B) receptor m RNA levels in lung. In thoracic aorta and the four heart chambers, ET( A) and ET(B) receptor mRNA levels were increased, but ET-1 mRNA levels were unchanged from air control levels. No change in ET-1 or ET recep tor mRNA levels was seen in organs perfused by the systemic vascular b ed, except in liver, where ET(A) receptor mRNA levels were decreased. The findings of concomitant increases in gene transcript levels for ET -1 and the ET(A) and ET(B) receptors in lung, but not in the great ves sels or any other organ examined, are consistent with the hypothesis t hat increased ET-1 synthesis in the lung contributes to pulmonary vasc ular remodeling and the maintenance of chronic hypoxic pulmonary hy pe rtension.