Abstract
Objective:Because changes in blood oxygenation acutely alter vascular tone, we explored a possible modulation of nitric oxide-induced vasodilation (nitrovasodilation) by oxygen. Methods:We studied the effects of manipulation of tissue oxygenation on renal parenchymal nitric oxide (NO) with a selective NO electrode placed in the well-oxygenated renal cortex or in the physiologically hypoxemic outer medulla. Results:In the cortex, as expected, NO signals fell in response to the NO synthase (NOS) inhibitor L-NAME. By contrast, in the outer medulla, NO signals paradoxically rose following NOS inhibition, known to intensify local hypoxia. Other manipulations that intensify outer medullary hypoxia (such as indomethacin or radiologic contrast media) increased local NO readings, while measures known to ameliorate outer medullary hypoxia (furosemide, L-arginine, hypotension) reduced regional NO readings. Conclusions:Oxygen appears to modulate NO bioavailability, in particular, in tissues with low ambient pO2, perhaps through enhanced binding to oxygenated hemoglobin. It is proposed that this phenomenon may participate in physiological microvascular regulation, with hypoxemia enhancing NO concentration, while hyperoxemia resulting in accelerated NO removal.