TY - JOUR T1 - Low Sodium Modifies the Vascular Effects of Angiotensin-Converting Enzyme Inhibitor Therapy in Healthy Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1183 LP - 1189 DO - 10.1124/jpet.104.067272 VL - 310 IS - 3 AU - Menno J. A. Kocks AU - Simone Gschwend AU - Dick de Zeeuw AU - Gerjan Navis AU - Hendrik Buikema Y1 - 2004/09/01 UR - http://jpet.aspetjournals.org/content/310/3/1183.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -