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Low Sodium Modifies the Vascular Effects of Angiotensin-Converting Enzyme Inhibitor Therapy in Healthy Rats
Low dietary sodium (LS) increases the effect of angiotensin-converting enzyme (ACE) inhibitor therapy in patients and experimental models, but mechanisms underlying this enhanced efficacy are largely unknown. Because the benefits of ACE inhibition are mediated to a considerable extent by their effec...
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Published in: | The Journal of pharmacology and experimental therapeutics 2004-09, Vol.310 (3), p.1183-1189 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Low dietary sodium (LS) increases the effect of angiotensin-converting enzyme (ACE) inhibitor therapy in patients and experimental
models, but mechanisms underlying this enhanced efficacy are largely unknown. Because the benefits of ACE inhibition are mediated
to a considerable extent by their effect on the vasculature, we studied whether low sodium alters the vascular effects of
ACE inhibition. Baseline functional and morphological characteristics, and endothelium-dependent and -independent dilatory
responses were studied in isolated perfused small intrarenal and mesenteric arteries obtained from control rats (CON), rats
on LS, lisinopril-treated rats (CON-LIS), or rats treated with lisinopril during LS (LS-LIS). We found, first, that LS-LIS
compared with CON-LIS enhances blood pressure reduction. Second, interlobar renal arteries had increased lumen diameter and
reduced adrenergic contractility in CON-LIS compared with CON, without additional effects of LS. In contrast, mesenteric arteries
were not altered in CON-LIS compared with CON, but became triggered for increased myogenic and adrenergic constriction in
LS-LIS. Third, LS-LIS decreased acetylcholine (ACh)-induced vasodilation in both mesenteric and renal arteries compared with
CON-LIS. During the latter condition, opposite prostaglandins are involved in the endothelial function of the two different
vascular beds, i.e., increased involvement of contractile prostaglandins in ACh-induced vasodilatation in renal arteries,
versus dilatory prostaglandins in mesenteric arteries. Whether cause or consequence of the enhanced blood pressure response,
our data demonstrate a modifying effect of dietary sodium on vascular effects of ACE inhibition. These findings provide a
rationale for further studies addressing the mechanism-of-actions of our therapies to find additional strategies to improve
therapy response. |
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ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.104.067272 |