Summary
The (Na+, K+)-ATPase activity operative in rabbit aortic intima-media incubated with normal plasma levels of glucose and myo-inositol (70 μmol/l) is decreased when the glucose content of the medium is raised from 5 to 10 mmol/l or higher; this effect is prevented by aldose reductase inhibitors and by raising the myo-inositol content of the medium to 500 μmol/l. The decrease in (Na+, K+)-ATPase activity results from the loss of a component normally regulated (stimulated) by endogenously released adenosine through a receptor that stimulates phosphatidylinositol turnover in a discrete pool. The replenishment of this phosphatidylinositol pool selectively requires myo-inositol transport and is inhibited when increased polyol pathway activity impairs myo-inositol transport at a normal plasma level. Adenosine is a vasodilator, some endothelium-released vasodilators modulate the responses to vasoconstrictors by stimulating an increase in (Na+, K+)-ATPase activity in vascular smooth muscle. Whether adenosine mediates this effect in angiotensin II or norepinephrine-stimulated aorta was examined. Angiotensin II (100 nmol/l) and norepinephrine (1 μmol/l) evoked marked increases in (Na+, K+)-ATPase activity in aortic intima-media incubated with 5 mmol/l glucose and 70 μmol/l myo-inositol, which were inhibited when adenosine deaminase was added or the medium myo-inositol omitted to inhibit myo-inositol transport. Raising the medium glucose to 30 mmol/l inhibited the angiotensin II and norepinephrine evoked increases in (Na+, K+)-ATPase activity, and this was prevented when tolrestat (10 μmol/l) was added or the myo-inositol content of the medium was raised from 70 to 500 μmol/l. Hyperglycaemia causes decreased (Na+, K+)-ATPase activity prevented by aldose reductase inhibitors and by raising plasma myo-inositol by a mechanism which inhibits an adenosine-(Na+, K+)-ATPase regulatory system, which modulates the responses to angiotensin II and norepinephrine in some blood vessels.
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Simmons, D.A., Winegrad, A.I. Mechanisms in rabbit aorta for hyperglycaemia-induced alterations in angiotensin II and norepinephrine effects. Diabetologia 35, 725–729 (1992). https://doi.org/10.1007/BF00429091
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DOI: https://doi.org/10.1007/BF00429091