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Mechanism of hypoxia/reoxygenation damage in rat cerebral arterioles
Author(s) -
Dietrich Hans H,
Xiang Chuanxi,
Dacey Ralph G
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1220-b
Subject(s) - hypoxia (environmental) , nitric oxide , ischemia , vasoconstriction , chemistry , potassium channel , cerebral circulation , adenosine , perfusion , calcium , medicine , anesthesia , endocrinology , pharmacology , oxygen , biochemistry , organic chemistry
Background: It is not known if Ischemia/Reperfusion (I/R) directly impairs cerebral microvascular regulation. Such impairment could contribute to regional hypoperfusion as observed after I/R. Methods: Cerebral arterioles were isolated, cannulated and their internal diameter monitored with a video microscope. Vasomotor responses to adenosine tri‐phosphate (ATP) were obtained before and/or after 60 to 120 min. of hypoxia (PO 2 < 5 mmHg) with rapid normoxic reoxygenation (H/RO) in the presence or absence of inhibitors. Results: Arterioles significantly constricted during hypoxia. Reoxygenation resulted in a transient dilation followed by a significant vasoconstriction which lasted more than 120 min. Dilation to ATP was significantly decreased. Application of oxygen radial scavenger MnTBAP or calcium sensitive potassium channel activators restored dilation to ATP but not inhibition of nitric oxide synthase. Conclusions: H/RO directly impairs cerebral arteriolar regulation causing prolonged constriction and reduced dilation which could contribute to the hypoperfusion observed after ischemia/reperfusion and promote neuronal damage. possibly via production of reactive oxygen species (ROS) and subsequent inhibition of calcium activated potassium channels. ROS scavenging or potassium channel openers rescued the vessel response. NIH HL57540 (HHD) and NS30555 (RGD and HHD).