title: Hypoxic Vasospasm Mediated by cIMP: When Soluble Guanylyl Cyclase Turns Bad.
abstract: In a number of isolated blood vessel types, hypoxia causes an acute contraction that is dependent on the presence of nitric oxide and activation of soluble guanylyl cyclase. It is more pronounced when the preparations are constricted and is therefore termed hypoxic augmentation of vasoconstriction. This hypoxic response is accompanied by increases in the intracellular level of inosine 5'-triphosphate and in the synthesis of inosine 3',5'-cyclic monophosphate (cIMP) by soluble guanylyl cyclase. The administration of exogenous cIMP or inosine 5'-triphosphate causes augmented vasoconstriction to hypoxia. Furthermore, the vasoconstriction evoked by hypoxia and cIMP is associated with increased activity of Rho kinase (ROCK), indicating that cIMP may mediate the hypoxic effect by sensitizing the myofilaments to Ca through ROCK. Hypoxia is implicated in exaggerated vasoconstriction in the pathogenesis of coronary artery disease, myocardial infarction, hypertension, and stroke. The newly found role of cIMP may help to identify unique therapeutic targets for certain cardiovascular disorders.
authors.affiliation: *Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China; †State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing, China; ‡Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; and §State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Chen
authors.forename: Susan W S
authors.initials: SW
authors.lastname: Leung
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D020013:Calcium Signaling; D007289:Cyclic IMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000503:physiopathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015290:Second Messenger Systems; D000071756:Soluble Guanylyl Cyclase; D013035:Spasm / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D014661:Vasoconstriction; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D007289:Cyclic IMP; D054460:rho-Associated Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase