title: Alteration by lipopolysaccharide of the relationship between intracellular calcium levels and contraction in rat mesenteric artery.
abstract: 1. The aim of this work was to investigate the effect of lipopolysaccharide (LPS) treatment on the relationship between the cytosolic Ca2+ ion concentration ([Ca2+]i) and contraction in rat resistance arteries, and the involvement of the L-arginine-nitric oxide (NO)-guanosine 3'-5' cyclic monophosphate (cyclic GMP) pathway in these effects. 2. [Ca2+]i and tension were simultaneously recorded in small mesenteric arteries removed from rats 4 h after intraperitoneal injection of E. coli LPS (30 mg kg-1) or solvent. Cyclic GMP was assayed in vessels submitted to identical treatments. 3. Basal [Ca2+]i was higher in vessels from LPS-treated rats compared to controls. LPS did not modify the concentration-contraction curve of noradrenaline. However, the increase in basal [Ca2+]i produced by LPS resulted in a shift of the noradrenaline [Ca2+]i-contraction curve to higher [Ca2+]i concentrations. 4. L-Arginine (300 microM) relaxed noradrenaline (10 microM) pre-contracted arteries from LPS-treated but not from control rats. This effect of L-arginine was reversed by two inhibitors of NO synthase: N omega-nitro-L-arginine-methyl-ester (L-NAME, 1 mM) and S-methyl-isothiourea (SMT, 0.1 mM). Both the relaxing effect of L-arginine and its reversal by L-NAME or SMT occurred without any change in [Ca2+]i. 5. LPS treatment did not modify the cyclic GMP content of the small mesenteric arteries. In arteries removed from LPS-treated rats but not from controls, addition of L-arginine (300 microM) was associated with a significant increase in cyclic GMP content, an effect which was prevented by both L-NAME (1 mM) and SMT (0.1 mM). 6. L-NAME (1 mM) produced a greater reduction in cyclic GMP content than SMT (0.1 mM) in control vessels exposed to L-arginine (300 microM). Under the same conditions, SMT produced a larger decrease in cyclic GMP level than L-NAME in arteries taken from LPS-treated rats, consistent with selective inhibition by SMT of the inducible NO-synthase after LPS. 7. These results show that LPS produced two effects in small mesenteric arteries: (i) alterations in Ca2+ handling and a decreased sensitivity of myofilaments to Ca2+, (ii) induction of NO-synthase activity resulting in exogenous L-arginine-dependent production of NO and cyclic GMP accumulation. Both effects are likely to be involved in the hyporeactivity induced by LPS in resistance arteries.
authors.affiliation: Laboratoire de Pharmacologie et Physiopathologie Cellulaires, Université Louis Pasteur de Strasbourg, URA CNRS 600 Faculté de Pharmacie, Illkirch, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Martínez
authors.forename: B
authors.initials: B
authors.lastname: Muller
authors.forename: J C
authors.initials: JC
authors.lastname: Stoclet
authors.forename: R
authors.initials: R
authors.lastname: Andriantsitohaina
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009609:Nitrous Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D001120:Arginine; D006152:Cyclic GMP; D009609:Nitrous Oxide; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine