Ni Z, Bemanian S, Kivlighn S D, Vaziri N D
Department of Medicine, University of California, Irvine, USA.
Kidney Int. 1998 Jul;54(1):188-92. doi: 10.1046/j.1523-1755.1998.00987.x.
We have recently demonstrated that prolonged hypobaric hypoxia can lead to a hematocrit-independent sustained arterial hypertension (HTN) in genetically normotensive Sprague-Dawley rats. The rise in blood pressure in the hypoxic animals was accompanied by a marked but transient increase in plasma endothelin level. In addition, hypoxia has been shown to decrease nitric oxide (NO) production by cultured endothelial cells. This study was designed to test the hypothesis that hypoxia-induced HTN may be mediated by increased endothelin and/or decreased NO production.
Blood pressure, plasma endothelin and urinary NO metabolites (NOx)were monitored in rats during a 24-hour exposure to hypobaric hypoxia (air pressure = 390 mm Hg). The results were compared with hypoxia (air pressure = 390 mm Hg). The results were compared with those obtained in animals maintained under normoxic condition (control group). To test the possible role of excess endothelin and depressed NO production, the studies were repeated using subgroups of animals treated with either an endothelin receptor ET-A/B blocker (L-754,142) or L-arginine.
The untreated hypoxic group exhibited a threefold rise in plasma endothelin and a threefold fall in urinary NOx, prior to the onset of HTN. Endothelin receptor blockade led to a further fall in urinary NOx excretion and failed to mitigate HTN. In contrast, L-arginine supplementation improved the urinary NOx excretion and prevented HTN. Neither therapy affected the hypoxia-induced erythrocytosis.
We conclude that hypoxia-induced HTN is associated with depressed NO production and can be mitigated by L-arginine supplementation.
