title: Low sodium modifies the vascular effects of angiotensin-converting enzyme inhibitor therapy in healthy rats.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. h.buikema@med.rug.nl
authors.forename: Menno J A
authors.initials: MJ
authors.lastname: Kocks
authors.forename: Simone
authors.initials: S
authors.lastname: Gschwend
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Hendrik
authors.initials: H
authors.lastname: Buikema
mesh_terms: D000109:Acetylcholine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D018565:Food-Drug Interactions; D017706:Lisinopril / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011453:Prostaglandins; D012982:Sodium, Dietary; D012964:Sodium; D017706:Lisinopril; D000109:Acetylcholine