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Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans
Author(s) -
Holowatz Lacy A.,
Santhanam Lakshmi,
Webb Alanah,
Berkowitz Dan E.,
Kenney W. Larry
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.203935
Subject(s) - arginase , vasoprotective , nitric oxide , vasodilation , medicine , atorvastatin , downregulation and upregulation , endocrinology , pharmacology , arginine , chemistry , biochemistry , amino acid , gene
Non‐technical summary A high concentration of cholesterol in the blood, known as hypercholersterolaemia, in the absence of overt atherosclerotic disease induces changes throughout the circulation including an inability to fully respond to vasodilatory stimuli. Here we show that skin blood flow responses are reduced in hypercholersterolaemic men and women partly due to an upregulation of the arginase pathway. Arginase competes for the common substrate l ‐arginine for the synthesis of the vasoprotective molecule nitric oxide. After 3 months of oral atrovastatin (cholesterol lowering medication) intervention, arginase activity was decreased and skin blood flow responses resembled those of healthy men and women. This suggests that upregulated arginase contributes to decreased vasoreactivity in hyperocholesterolaemic humans and that atrovastatin therapy restores functional vasodilatory properties by decreasing arginase activity.