Differential impacts of brain stem oxidative stress and nitrosative stress on sympathetic vasomotor tone

Based on work-done in the rostral ventrolateral medulla (RVLM), this review presents four lessons learnt from studying the differential impacts of oxidative stress and nitrosative stress on sympathetic vasomotor tone and their clinical and therapeutic implications. The first lesson is that an increase in sympathetic vasomotor tone because of augmented oxidative stress in the RVLM is responsible for the generation of neurogenic hypertension. On the other hand, a shift from oxidative stress to nitrosative stress in the RVLM underpins the succession of increase to decrease in sympathetic vasomotor tone during the progression towards brain stem death. The second lesson is that, by having different cellular sources, regulatory mechanisms on synthesis and degradation, kinetics of chemical reactions, and downstream signaling pathways, reactive oxygen species and reactive nitrogen species should not be regarded as a singular moiety. The third lesson is that well-defined differential roles of oxidative stress and nitrosative stress with distinct regulatory mechanisms in the RVLM during neurogenic hypertension and brain stem death clearly denote that they are not interchangeable phenomena with unified cellular actions. Special attention must be paid to their beneficial or detrimental roles under a specific disease or a particular time window of that disease. The fourth lesson is that, to be successful, future antioxidant therapies against neurogenic hypertension must take into consideration the much more complicated picture than that presented in this review on the generation, maintenance, regulation or modulation of the sympathetic vasomotor tone. The identification that the progression towards brain stem death entails a shift from oxidative stress to nitrosative stress in the RVLM may open a new vista for therapeutic intervention to slow down this transition. (C) 2019 Published by Elsevier Inc.