Endothelin-1 mediates nitro-L-arginine vasoconstriction of hypertensive rat lungs

The American Journal of Physiology
M MuramatsuI F McMurtry

Abstract

Inhibition of endothelium-derived nitric oxide (NO) synthesis by L-arginine analogs such as nitro-L-arginine (L-NNA) elicits marked precapillary vasoconstriction in lungs from rats with chronic hypoxia-induced pulmonary hypertension. To investigate the role of endogenous endothelin (ET)-1 in L-NNA-induced vasoconstriction, we tested, in salt solution-perfused hypertensive lungs isolated from chronically hypoxic (3-4 wk at barometric pressure = 410 mmHg) adult male rats, if the pressor responses to L-NNA and exogenous ET-1 were inhibited by either separate or combined ETA and ETB receptor blockade. Whereas only combined pretreatment with 5 microM BQ-123 (selective ETA receptor blocker) and 5 microM BQ-788 (selective ETB receptor blocker) inhibited the response to 100 microM L-NNA, the response to 10 nM ET-1 was reduced by both BQ-123 alone and the combined blockers. Because exogenous ET-1 causes postcapillary vasoconstriction in salt solution-but not blood-perfused normotensive rat lungs, we next compared effects of ETA and ETB receptor blockade on L-NNA and ET-1 vasoconstrictions in blood-perfused hypertensive lungs. In this case, the combined but not the separate effects of BQ-123 and BQ-788 inhibited the responses to both L-N...Continue Reading

Citations

Sep 10, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Tetsutaro NagaokaMasahiko Oka
Jan 3, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·T C RestaB R Walker
Mar 11, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·K SatoI F McMurtry
Oct 4, 2000·Physiological Reviews·V Hampl, J Herget
Jan 11, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Yoshiteru MorioIvan F McMurtry
Jun 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Elena V BalyakinaBarbara Meyrick
Feb 3, 2012·Physiological Reviews·J T SylvesterJeremy P T Ward

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