N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent relaxation in the rabbit renal artery: effect of hypercholesterolemia.
Studies were designed to compare the N(G)-nitro-L-arginine- and indomethacin-resistant, endothelium-dependent relaxation to acetylcholine in isolated renal artery rings from normal and cholesterol-fed rabbits. It was assumed that the resistant part in response to acetylcholine is mediated by the endothelial-derived hyperpolarizing factor (EDHF). Rabbits were fed normal (n = 15) or cholesterol enriched chow (n = 13, 1% cholesterol for 4 weeks, 0.5% for 12 weeks). In organ chamber experiments, renal artery rings were precontracted with 0.1-1 microM phenylephrine or 35 mM KCl, and relaxed with acetylcholine (0.001-10 microM) in the presence of 10 microM indomethacin. Studies were performed in the presence or absence of: 100 microM N(G)-nitro-L-arginine (L-NOARG) to inhibit the nitric oxide pathway, 100 nM charybdotoxin (CTX) or 1 mM tetrabutylammonium (TBA) to inhibit Ca2+-activated K+ channels, and 100 microM SKF 525a to inhibit cytochrome P450 monoxygenase pathway. In normal arteries, L-NOARG partially inhibited acetylcholine-induced relaxation. The resistant part was almost abolished when the arteries were depolarized with KCl, or when L-NOARG was combined with either CTX, TBA or SKF 525a. In arteries from hypercholesterolemic animals, the relaxation to acetylcholine was only slightly impaired as compared to normal animals. However, in comparison to arteries from normal animals, the L-NOARG-resistant part of acetylcholine-induced endothelium-dependent relaxation was enhanced. It is speculated that differences in the balance between nitric oxide (NO)- and EDHF-mediated control of vascular tone may maintain acetylcholine-induced vasodilatation of the renal artery in hypercholesterolemia.
Brandes
R P
RP
Division of Cardiology, Hannover Medical School, Germany.
Behra
A
A
Lebherz
C
C
Böger
R H
RH
Bode-Böger
S M
SM
Phivthong-Ngam
L
L
Mügge
A
A
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D019335:Nitroarginine / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects / Q000503:physiopathology*
D002791:Cholesterol, Dietary; D000644:Quaternary Ammonium Compounds; D019335:Nitroarginine; D011335:Proadifen; C009405:tetrabutylammonium; D007213:Indomethacin