N-G-NITRO-L-ARGININE-RESISTANT AND INDOMETHACIN-RESISTANT ENDOTHELIUM-DEPENDENT RELAXATION IN THE RABBIT RENAL-ARTERY - EFFECT OF HYPERCHOLESTEROLEMIA

Studies were designed to compare the NG-nitro-L-arginine-and indometha cin-resistant, endothelium-dependent relaxation to acetylcholine in is olated renal artery rings from normal and cholesterol-fed rabbits. It was assumed that the resistant part in response to acetylcholine is me diated by the endothelial-derived hyperpolarizing factor (EDHF). Rabbi ts were fed normal (n = 15) or cholesterol enriched chow (n = 13, 1% c holesterol for 4 weeks, 0.5% for 12 weeks). In organ chamber experimen ts, renal artery rings were precontracted with 0.1-1 mu M phenylephrin e or 35 mM KCl, and relaxed with acetylcholine (0.001-10 mu M) in the presence of 10 mu M indomethacin. Studies were performed in the presen ce or absence of: 100 mu M N-G-nitro-L-arginine (L-NOARG) to inhibit t he nitric oxide pathway, 100 nM charybdotoxin (CTX) or 1 mM tetrabutyl ammonium (TBA) to inhibit Ca2+-activated K+ channels, and 100 mu M SKF 525a to inhibit cytochrome P-450 monoxygenase pathway. In normal arte ries, L-NOARG partially inhibited acetylcholine-induced relaxation. Th e resistant part was almost abolished when the arteries were depolariz ed with KCl, or when L-NOARG was combined with either CTX, TEA or SKF 525a. In arteries from hypercholesterolemic animals, the relaxation to acetylcholine was only slightly impaired as compared to normal animal s. However, in comparison to arteries from normal animals, the L-NOARG -resistant part of acetylcholine-induced endothelium-dependent relaxat ion was enhanced. It is speculated that differences in the balance bet ween nitric oxide (NO)-and EDHF-mediated control of vascular tone may maintain acetylcholine-induced vasodilatation of the renal artery in h ypercholesterolemia. (C) 1997 Elsevier Science Ireland Ltd.