Introduction: Hemoglobin (HbFe(II)) plays a crucial role in transporting oxygen to tissues for metabolic needs. However, this protein isn't just an oxygen carrier; it also regulates vascular tone and inflammation by its redox coupling with methemoglobin (HbFe(III)). Methemoglobin's oxidized form, Fe (III), possesses the potential to produce water from oxygen as a free energy reaction. It functions as a nitrite reductase, regulating the oxygen level in the blood and controlling vascular tone by generating nitric oxide from nitrite, thereby increasing blood flow when oxygenated hemoglobin decreases. If methemoglobin can't be reduced, it leads to the dissociation of tetrameric hemoglobin into αβ dimers, releasing heme and iron into circulation. Methods: The study involved Golden Syrian Hamsters with dorsal skin fold window chambers, observing acute methemoglobin effects via hypovolemic infusion (10% of the animal’s blood volume) compared to human hemoglobin and a lactated ringer's control. Microhemodynamics, mean arterial pressure, heart rate, blood gases, and blood properties were measured. Results: Methemoglobin did not significantly affect MAP and HR but increased arteriole diameters by 5% and venule diameter by 15% compared to baseline. However, it caused a 50% reduction in functional capillary density compared to baseline, alongside significant cardiac and kidney inflammation. Conclusion: The study concludes that a hypovolemic infusion of methemoglobin induces vasoreactivity but results in poor microcirculatory pressure and inflammation in vital organs. This demonstrates the delicate balance and potential adverse effects associated with alterations in the hemoglobin redox state and highlights the importance of maintaining its balance for vascular and organ health. Project number: R01HL159862 Project number: R01HL162120. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.