title: Isometric contraction increases endothelial nitric oxide synthase activity via a calmodulin antagonist-sensitive pathway in rat aorta.
abstract: In this work, the possibility that isometric contraction activates endothelial nitric oxide synthase (eNOS) in a calcium/calmodulin (Ca2+/CaM)-dependent manner was examined in rat thoracic aorta. Step-wise stable contractile responses (precontractions) to phenylephrine were obtained in endothelium-intact and endothelium-denuded aortic rings. The subsequent addition of the NO synthase inhibitor, N(G)nitro-l-arginine methyl ester (l-NAME), or the soluble guanylyl cyclase inhibitor, ODQ, further augmented precontractions in a concentration-dependent manner. The amplitude of l-NAME- and ODQ-induced increases in tone were dependent on the level of precontraction; the maximal increments for l-NAME and ODQ were observed in arteries precontracted with phenylephrine at 67% of its maximal effect. Likewise, in endothelium-intact non-contracted arteries, l-NAME and ODQ induced small but significant increases in tone. Neither l-NAME nor ODQ had any effect in endothelium-denuded preparations. In endothelium-intact aortic rings precontracted with high K+ solutions, l-NAME also elicited supplementary contractions dependent on precontraction level. The CaM antagonist, calmidazolium, inhibited in a concentration-dependent, noncompetitive, manner the effects of l-NAME on the tone of endothelium-intact phenylephrine-precontracted aortic rings. These results suggest that isometric contraction increases the activity of eNOS by means of the Ca2+/CaM complex in rat aorta.
authors.affiliation: Postgraduate and Investigation Section, Superior Medicine School, National Polytechnic Institute. Mexico, DF, Mexico.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: López
authors.forename: Carlos
authors.initials: C
authors.lastname: Castillo
authors.forename: Enrique F
authors.initials: EF
authors.lastname: Castillo
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000071756:Soluble Guanylyl Cyclase
chemical_list: D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; D018160:Receptors, Cytoplasmic and Nuclear; C031938:calmidazolium; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester