WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

Author(s): Writing Group Members; Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; Das, Sandeep R; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Isasi, Carmen R; Jimenez, Monik C; Judd, Suzanne E; Kissela, Brett M; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Magid, David J; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Muntner, Paul; Mussolino, Michael E; Nasir, Khurram; Neumar, Robert W; Nichol, Graham; Palaniappan, Latha; Pandey, Dilip K; Reeves, Mathew J; Rodriguez, Carlos J; Rosamond, Wayne; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; American Heart Association Statistics Committee; Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

/pdf/the-nox-family-of-ros-generating-nadph-oxidases-physiology-zjc88zvh59.pdf

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

2018 ESC/ESH Guidelines for the management of arterial hypertension.

Endothelin-1 (ET1) is a potent vasoconstrictor peptide implicated in the cerebrovascular alterations occurring in stroke, subarachnoid hemorrhage, and brain trauma. Brain or circulating levels of E...

Circulating Endothelin-1 Alters Critical Mechanisms Regulating Cerebral Microcirculation

Effects of aminoguanidine on cerebral ischemia in mice: comparison between mice with and without inducible nitric oxide synthase gene.

We have previously demonstrated that topical cortical application of nitro-L-arginine (L-NA), a potent inhibitor of nitric oxide (NO) synthesis, attenuates resting cerebral blood flow (CBF) and the cerebrovasodilation elicited by hypercapnia. In this study, we sought to determine whether these cerebrovascular effects of L-NA are secondary to a depression in cerebral metabolism. Rats were anesthetized (chloralose, 80 mg/kg) and artificially ventilated. Arterial pressure and blood gases were monitored. The frontal cortex was exposed and superfused with normal Ringer (pH 7.3-7.4; 37 degrees C) or with Ringer containing L- or D-NA. CBF or cerebral glucose utilization (CGU) was measured autoradiographically using the [14C]iodoantipyrine or 2-[14C]deoxy-D-glucose method, respectively. Application of normal Ringer did not affect CBF at the site of superfusion (n = 5; P > 0.05, paired t test). Application of L-NA (1 mM; n = 5), but not D-NA (1 mM; n = 6), attenuated resting CBF by 33 +/- 5% (P 0.05). Resting CBF and the CBF response to hypercapnia were largely unaffected in brain regions outside the field of superfusion. In contrast to hypercapnia, L-NA (1 mM) did not attenuate the increases in CBF elicited by topical application of papaverine (10-1,000 microM; n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting cerebral metabolism

The vasodilation elicited in cerebral cortex by stimulation of the cerebellar fastigial nucleus (FN) is mediated by input pathways coming from the basal forebrain. We studied whether these pathways mediate the cortical vasodilation via a direct action on local blood vessels or via interposed local neurons. Neurons were destroyed in the primary sensory cortex by local microinjection of the excitotoxin ibotenic acid (IBO) (10 micrograms/l microliter). Five days later rats were anesthetized (alpha-chloralose), paralyzed, and ventilated. Arterial pressure and blood gases were controlled, and FN was stimulated electrically. Local cerebral blood flow (LCBF) was measured using the [14C]iodoantipyrine technique with autoradiography. Five days after IBO, neurons were destroyed in a restricted cortical area, and afferent fibers and terminals were preserved. The selectivity of the neuronal loss was established by histological and biochemical criteria and by transport of horseradish peroxidase from or into the lesion. Within the lesion, resting LCBF (n = 7) was unaffected, but the increase in LCBF evoked from the FN was abolished (P greater than 0.05); n = 6). In contrast the vasodilation elicited by hypercapnia (arterial CO2 partial pressure = 62.7 +/- 3; n = 5) was preserved. In the rest of the brain the vasodilation elicited from FN was largely unaffected. We conclude that the vasodilation evoked from FN in cerebral cortex depends on the integrity of a restricted population of local neurons that interact with the local microvasculature.

Role of local neurons in cerebrocortical vasodilation elicited from cerebellum

Sublethal injurious stimuli induce tolerance to subsequent lethal insults, a phenomenon termed preconditioning Inducible nitric oxide synthase (iNOS) is essential for the preconditioning induced by transient bilateral common carotid artery occlusion (BCCAO) or by systemic administration of the endotoxin lipopolysaccharide (LPS) We used a model of brain injury produced by neocortical injection of N-methyl-D-aspartate (NMDA) to investigate the mechanisms by which iNOS-derived nitric oxide (NO) contributes to tolerance induced by LPS or BCCAO We found that the tolerance is blocked by the iNOS inhibitor aminoguanidine, is not observed in iNOS-null mice, and is rescued by the NO donor DTPA NONOate Lipopolysaccharide failed to induce preconditioning in mice lacking the nox2 subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, suggesting that superoxide derived from NADPH oxidase is needed for the induction of the tolerance Because superoxide reacts with NO to form peroxynitrite, we investigated the role of peroxynitrite We found that LPS induces the peroxynitrite marker 3-nitrotyrosine in cortical neurons and that the peroxynitrite decomposition catalyst FeTPPS abolishes LPS-induced preconditioning These results suggest that the protective effect of iNOS-derived NO is mediated by peroxynitrite formed by the reaction of NO with NADPH oxidase-derived superoxide Thus, peroxynitrite, in addition to its well-established deleterious role in ischemic brain injury and neurodegeneration, can also be beneficial by inducing tolerance to excitotoxicity

https://journals.sagepub.com/doi/pdf/10.1038/sj.jcbfm.9600449

Costantino Iadecola

Papers

Circulating Endothelin-1 Alters Critical Mechanisms Regulating Cerebral Microcirculation

Effects of aminoguanidine on cerebral ischemia in mice: comparison between mice with and without inducible nitric oxide synthase gene.

Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting cerebral metabolism

Role of local neurons in cerebrocortical vasodilation elicited from cerebellum

INOS-derived NO and nox2-derived superoxide confer tolerance to excitotoxic brain injury through peroxynitrite