title: Hemoglobin induced NO/cGMP suppression Deteriorate Microcirculation via Pericyte Phenotype Transformation after Subarachnoid Hemorrhage in Rats.
abstract: Subarachnoid hemorrhage (SAH) usually results from ruptured aneurysm, but how leaked hemoglobin regulates the microcirculation in the pathophysiology of early brain injury after SAH is still unclear. In the present study, we sought to investigate the role and possible mechanism of hemoglobin induced pericyte phenotype transformation in the regulation of microcirculation after SAH. Endovascular perforation SAH rat model, brain slices and cultured pericytes were used, and intervened with endothelial nitric oxide synthase (eNOS) antagonist L-NNA and its agonist scutellarin, hemoglobin, DETA/NO (nitric oxide(NO) donor), PITO (NO scavenger), 8-Br-cGMP (cGMP analog). We found modulating eNOS regulated pericyte α-SMA phenotype transformation, microcirculation, and neurological function in SAH rats. Modulating eNOS also affected eNOS expression, eNOS activity and NO availability after SAH. In addition, we showed hemoglobins penetrated into brain parenchyma after SAH. And hemoglobins significantly reduced the microvessel diameters at pericyte sites, due to the effects of hemoglobin inducing α-SMA expressions in cultured pericytes and brain slices via inhibiting NO/cGMP pathway. In conclusion, pericyte α-SMA phenotype mediates acute microvessel constriction after SAH possibly by hemoglobin suppressing NO/cGMP signaling pathway. Therefore, by targeting the eNOS and pericyte α-SMA phenotype, our present data may shed new light on the management of SAH patients.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.|Department of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Jinan Military General Hospital, Jinan, Shandong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Shilun
authors.initials: S
authors.lastname: Zuo
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Huaizhen
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015870:Gene Expression; D006454:Hemoglobins / Q000096:biosynthesis*; D008297:Male; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D015398:Signal Transduction; D013345:Subarachnoid Hemorrhage / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000199:Actins; D006454:Hemoglobins; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP