AI Article Synopsis
- Hypoxia leads to a strong contraction in specific blood vessels, requiring nitric oxide and soluble guanylyl cyclase activation, a phenomenon referred to as hypoxic augmentation of vasoconstriction.
- Inosine 5'-triphosphate and cIMP levels increase during this response, and adding these substances enhances the vasoconstriction caused by hypoxia.
- The involvement of Rho kinase suggests that cIMP helps the body respond to hypoxia by making muscle fibers more sensitive to calcium, indicating potential new therapeutic targets for cardiovascular diseases like coronary artery disease and hypertension.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461383 | PMC |
| http://dx.doi.org/10.1097/FJC.0000000000000167 | DOI Listing |
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Article Synopsis
- - Myoglobin was genetically modified by replacing histidine (His93) with cysteine to study how diatomic ligands like carbon monoxide (CO) and nitric oxide (NO) affect bonding and dynamics, using advanced spectroscopy techniques.
- - This mutation resulted in altered heme bonding and dynamics, which showed different behavior compared to the wild-type myoglobin but paralleled observations in soluble guanylate cyclase (sGC), particularly in how NO and CO interact.
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