High dietary sodium blunts affects of angiotensin-converting enzyme inhibition on vascular angiotensin I-to-angiotensin II conversion in rats.
High sodium intake blunts the efficacy of angiotensin (Ang)-converting enzyme (ACE) inhibition (ACEi), but the underlying mechanism is incompletely characterized. High sodium has been reported to increase vascular expression and vascular activity of ACE. To investigate whether high-dietary sodium-induced effects on vascular conversion of Ang I might be involved in the sodium-induced blunting of the response to ACEi, the authors studied the vasoconstrictor responses to Ang I and Ang II of isolated aortic rings from healthy rats on low dietary sodium (LS: 0.05% NaCl) and high dietary sodium (HS: 2.0% NaCl) after 3 weeks of ACEi (lisinopril 75 mg/L) or vehicle (CON). Blood pressure was similar in LS and HS in CON, but HS blunted the blood pressure response to ACEi. Functional conversion of Ang I was assessed as the difference in dose-response curves to Ang I and Ang II in parallel aortic rings. Sodium intake did not affect the dose-response curves to Ang I and Ang II in CON. In the ACEi groups, a significant difference was present between the curves for Ang I and Ang II on LS (deltaEC50, 6.7 nM; range, 2.2-13 nM; P < 0.01) but not on HS (deltaEC50: 1.3 nM; range, 0.0-4.1 nM, median [interquartile range], NS). Thus, HS blunts the ACEi-induced reduction of functional vascular Ang I conversion compared with LS. Whether the blunted functional vascular conversion is causally related to the blunted blood pressure response remains to be elucidated.
Department of Internal Medicine, Division of Nephrology, University of Groningen, The Netherlands. m.j.a.kocks@int.azg.nl
Menno J A
MJ
Kocks
Hendrik
H
Buikema
Simone
S
Gschwend
Frans
F
Boomsma
Dick
D
de Zeeuw
Gerjan
G
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D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D051381:Rats; D017208:Rats, Wistar; D012982:Sodium, Dietary / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D012982:Sodium, Dietary; D000804:Angiotensin II; D000803:Angiotensin I