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.

Brucella abortus nitric oxide metabolite regulates inflammasome activation and IL‐1β secretion in murine macrophages

“…The preincubation of cells with l ‐NAME or SNAP did not affect invasion or intracellular bacterial growth, as observed in Figure E. To further investigate the phenomenon of inhibition of IL‐1β secretion mediated by NO, we infected BMDMs with B. abortus in the presence or absence of bovine hemoglobin (Hg), a widely known NO scavenger . These results strengthen our findings shown in the Figure , since the preincubation with Hg increased IL‐1β secretion and strongly reduced NO 2 − detection in B. abortus ‐infected cells (Supporting Information Fig.…”

Pericytes in Brain Injury and Repair After Ischemic Stroke

“…There are two kinds of brain pericytes, namely granular pericytes and filamentous pericytes, in microvessels under electron microscopy [35]. These two populations of pericytes can be distinguished by the presence of lysosome-like granules in the cytoplasm [36]. Granular pericytes, which compose about 95% of the entire cerebral pericyte population [36], may serve as scavenger cells in the brain.…”

“…These two populations of pericytes can be distinguished by the presence of lysosome-like granules in the cytoplasm [36]. Granular pericytes, which compose about 95% of the entire cerebral pericyte population [36], may serve as scavenger cells in the brain.…”

“…demonstrated that neuronal activity and neurotransmitter glutamate could dilate pericytes and thus increase capillary diameter. This process was proved to be mediated by postaglandin (PG) E2 in a NO-dependent manner [36]. Apart from PGE2, signals of increased energy use, including lactate, adenosine, and low pH, can also relax pericytes.…”

Salvinorin A ameliorates cerebral vasospasm through activation of endothelial nitric oxide synthase in a rat model of subarachnoid hemorrhage

“…Hematoxylin and eosin staining showed that the inner elastic membrane appeared serrated and it was thickening in the basilar artery, which might be caused by the imbalance of vasoconstrictors and vasodilators. 8 NO is a diffusible factor and powerful vessel dilator, 30 which was suggested to reverse the effects of the ET-1-induced vasoconstriction. 7 In this study, SA administration increased the content of NO and decreased the concentration of ET-1.…”