Background Hypoxic vasodilation is a physiological response to low oxygen (O2) tension that increases blood supply to match metabolic demands. While this response has been characterized for more than 100 years, the underlying hypoxic sensing and effector signaling mechanisms remain uncertain. We have shown that deoxygenated myoglobin (deoxyMb) in the heart can reduce nitrite to nitric oxide (NO˙) and thereby contribute to cardiomyocyte NO˙ signaling during ischemia. Based on recent observations that Mb is expressed in the vasculature of hypoxia-tolerant fish, we hypothesized that endogenous nitrite may contribute to physiological hypoxic vasodilation via reactions with vascular Mb to form NO˙. Methods and Results We here show that Mb is expressed in vascular smooth muscle and contributes significantly to nitrite-dependent hypoxic vasodilation in vivo and ex vivo. The generation of NO˙ from nitrite reduction by deoxyMb activates canonical soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) signaling pathways. In vivo and ex vivo vasodilation responses, the reduction of nitrite to NO˙ and the subsequent signal transduction mechanisms were all significantly impaired in mice without myoglobin (Mb−/−). Hypoxic vasodilation studies in Mb, endothelial and inducible NO synthase knockout models (eNOS−/−, iNOS−/−) suggest that only Mb contributes to systemic hypoxic vasodilatory responses in mice. Conclusions Endogenous nitrite is a physiological effector of hypoxic vasodilation. Its reduction to NO˙ via the heme globin Mb enhances blood flow and matches O2 supply to increased metabolic demands under hypoxic conditions.

Lyme disease is a tick-borne spirochetal infection that may affect the heart. Cardiac manifestations include conduction disturbances and other pathologies of the heart. We report on a 37-year old male, who was admitted to the emergency department because of dizziness and generalized tiredness. Physical examination and the initial laboratory values revealed no abnormalities. The patient's electrocardiogram on admission revealed newly diagnosed bradycardia due to atrioventricular heart block. The ventricular heart rate was 35/min. The patient was admitted to the ICU. Lyme serology and Western blot were positive for Borrelia antibodies. After institution of antibiotic therapy with ceftriaxone, atrioventricular heart block resolved rapidly. We therefore have to assume that in this patient Lyme carditis was the cause of third-degree AV block.

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