title: Vascular smooth muscle contraction is an independent regulator of endothelial nitric oxide production.
abstract: This investigation was conducted to determine whether endothelial nitric oxide (NO) production is regulated by vascular smooth muscle contraction. Unperfused ring segments of rat aorta and mesenteric artery were studied using isometric tension recording (n = 6-8 in all experiments). Following a reference contraction to K+ 80 mM (100%), arteries were left either unstimulated or stimulated by different concentrations of K+ or prostaglandin F2alpha (PGF2alpha) to induce different levels of vascular precontraction. N(G)-nitro-L-arginine methyl ester (L-NAME 0.1-300 microM) or NS 2028 (0.03-3 microM), which is a new specific inhibitor of the NO-sensitive guanylate cyclase, was then added at increasing concentrations to evaluate endothelial NO production. L-NAME and NS 2028 produced a concentration-dependent vasoconstrictor response which was progressively enhanced with increasing levels of precontraction. For L-NAME, this amounted in aorta to (% of reference contraction): 35+/-1% and 105 +/- 4% (precontraction by K(+) 20 and 30 mM) and 22+/-1%, 89+/-1%, 138+/-1% and 146+/-2% (precontraction by PGF2alpha 0.5, 1, 2 and 3 microM). A similar coupling was found in the mesenteric artery. A precontraction as little as 2% was enough to trigger a vasoconstrictor response to L-NAME. In contrast, L-NAME and NS 2028 had no effect in non-contracted arteries, not even when passive mechanical stretch was increased by 100%. The results suggest (i) that endothelial NO formation is progressively increased with increasing vascular tone, and (ii) that vascular isometric contraction per se stimulates endothelial NO formation. It is concluded, that active vascular smooth muscle contraction is an independent regulator of endothelial NO production.
authors.affiliation: Department of Medicine B, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Bang
authors.forename: J E
authors.initials: JE
authors.lastname: Nielsen-Kudsk
authors.forename: N
authors.initials: N
authors.lastname: Gruhn
authors.forename: S A
authors.initials: SA
authors.lastname: Theilgaard
authors.forename: S P
authors.initials: SP
authors.lastname: Olesen
authors.forename: S
authors.initials: S
authors.lastname: Boesgaard
authors.forename: J
authors.initials: J
authors.lastname: Aldershvile
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014666:Vasomotor System / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; C111257:NS 2028; D010069:Oxadiazoles; D010078:Oxazines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester