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.
Kocks
Menno J A
MJ
Department of Internal Medicine, Division of Nephrology, University of Groningen, The Netherlands. m.j.a.kocks@int.azg.nl
Buikema
Hendrik
H
Gschwend
Simone
S
Boomsma
Frans
F
de Zeeuw
Dick
D
Navis
Gerjan
G
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