de Kreutzenberg Saula Vigili, Puato Massimo, Kiwanuka Edward, Del Prato Stefano, Pauletto Paolo, Pasini Leone, Tiengo Antonio, Avogaro Angelo
Department of Clinical and Experimental Medicine, Cattedra di Malattie del Metabolismo, University of Padova, Via Giustiniani 2, 35128 Padua, Italy.
Atherosclerosis. 2003 Jul;169(1):147-53. doi: 10.1016/s0021-9150(03)00153-9.
To evaluate the role of elevation of non-esterified fatty acids on forearm nitric oxide (NO) dependent and independent relaxation, four studies were performed in the forearms of 14 normals: (1). endothelium-dependent and -independent vasodilations were assessed during acetylcholine (Ach) and sodium nitroprusside (SNP) infusions; (2). flow-mediated vasodilation (FMD) was assessed; (3) .bradykinin (BK) was infused during NO and prostaglandin inhibition (NO clamp); (4). blood flow (FBF) was measured during Ouabain, a Na(+)/K(+) ATPase, and BaCl(2), rectifying potassium channel (K(IR)) blockers, respectively. All studies were performed before and after 120 min. Intralipid+heparin (high-NEFA) infusion. Ach-mediated FBF increase was lower at high-NEFA (332+/-34 vs. 436+/-44% at 45 microg l forearm(-1) min(-1); % of ratio infused: control arm P<0.05), while SNP response was similar. FMD did not differ before and during high-NEFA, which induced a blunted response of FBF during BK with or without NO clamp. Ouabain and BaCl(2)-mediated FBF inhibition was lower (P<0.01) at high-NEFA. During ouabain alone FBF decreased slightly.
High-NEFA exerts a negative role on both NO-dependent and independent vasodilations. The decrease in FBF, mediated by K(IR) inhibition, is blunted by high-NEFA: these substrates interfere with hemodynamic/metabolism coupling, possibly through the inhibition of these channels.
