Nitric oxide (NO) and asymmetric dimethylarginine (ADMA): their pathophysiological role and involvement in intracerebral hemorrhage

TY - JOUR

T1 - Nitric oxide (NO) and asymmetric dimethylarginine (ADMA): their pathophysiological role and involvement in intracerebral hemorrhage

AU - Li, Na

AU - Worthmann, Hans

AU - Deb-Chatterji, Milani

AU - Chen, Shufen

AU - Weissenborn, Karin

PY - 2011/6

Y1 - 2011/6

N2 - OBJECTIVE: Nitric oxide (NO) has a variety of functions in physiological systems, particularly in the vasculature and the central nervous system. Currently, the imbalance of the pathway involving nitric oxide, nitric oxide synthase, and asymmetric dimethylarginine (NO-NOS-ADMA) is increasingly discussed in connection with endothelial dysfunction. Knowledge about the role of this pathway in intracerebral hemorrhage (ICH), which represents the most devastating stroke subtype, is increasing but still sparse. This article aims to review the current knowledge about the role and metabolism of NO and ADMA. It will also address the role of the NO-NOS-ADMA pathway in ICH and delineate some questions that should be addressed by future studies.METHODS: A literature search regarding the data about NO, NOS, and ADMA and its role in ICH was conducted in PubMed.RESULTS: Experimental data from cell culture and animal models indicate that, after the occurrence of ICH, neuronal and inducible nitric oxide synthases (nNOS and iNOS) are both overexpressed and uncoupled through the induction of blood compound metabolites, including thrombin and inflammatory mediators. ADMA, the most potent endogenous inhibitor of NOS, is also overproduced following dysregulation of its metabolizing enzymes. Dysfunction of the NO-NOS-ADMA pathway results in cell death, blood-brain barrier (BBB) disruption, and brain edema via different pathological mechanisms. However, the available data from clinical studies are still rare and partially contradictory.CONCLUSION: Experimental data suggest an important role for the NO-NOS-ADMA pathway for secondary injury after ICH. Since the literature shows contradictory results, further studies are needed to address current confusion.

AB - OBJECTIVE: Nitric oxide (NO) has a variety of functions in physiological systems, particularly in the vasculature and the central nervous system. Currently, the imbalance of the pathway involving nitric oxide, nitric oxide synthase, and asymmetric dimethylarginine (NO-NOS-ADMA) is increasingly discussed in connection with endothelial dysfunction. Knowledge about the role of this pathway in intracerebral hemorrhage (ICH), which represents the most devastating stroke subtype, is increasing but still sparse. This article aims to review the current knowledge about the role and metabolism of NO and ADMA. It will also address the role of the NO-NOS-ADMA pathway in ICH and delineate some questions that should be addressed by future studies.METHODS: A literature search regarding the data about NO, NOS, and ADMA and its role in ICH was conducted in PubMed.RESULTS: Experimental data from cell culture and animal models indicate that, after the occurrence of ICH, neuronal and inducible nitric oxide synthases (nNOS and iNOS) are both overexpressed and uncoupled through the induction of blood compound metabolites, including thrombin and inflammatory mediators. ADMA, the most potent endogenous inhibitor of NOS, is also overproduced following dysregulation of its metabolizing enzymes. Dysfunction of the NO-NOS-ADMA pathway results in cell death, blood-brain barrier (BBB) disruption, and brain edema via different pathological mechanisms. However, the available data from clinical studies are still rare and partially contradictory.CONCLUSION: Experimental data suggest an important role for the NO-NOS-ADMA pathway for secondary injury after ICH. Since the literature shows contradictory results, further studies are needed to address current confusion.

KW - Animals

KW - Arginine

KW - Cerebral Hemorrhage

KW - Humans

KW - Nitric Oxide

KW - Nitric Oxide Synthase

KW - Journal Article

KW - Review

U2 - 10.1179/016164111X13007856084403

DO - 10.1179/016164111X13007856084403

M3 - SCORING: Journal article

C2 - 21669125

VL - 33

SP - 541

EP - 548

IS - 5

ER -