TY - JOUR
T1 - Isometric contraction increases endothelial nitric oxide synthase activity via a calmodulin antagonist-sensitive pathway in rat aorta
AU - López, Ruth M.
AU - Castillo, Carlos
AU - Castillo, Enrique F.
N1 - Funding Information:
This work was supported by Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional (SIP-IPN); Comisión de Operación y Fomento de Actividades Académicas del IPN (COFAA); Consejo Nacional de Ciencia y Tecnología (CONACYT). The authors thank Ms. Lourdes Ramírez Pichardo for technical assistance.
PY - 2009/1
Y1 - 2009/1
N2 - 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, NGnitro-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.
AB - 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, NGnitro-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.
KW - Calmodulin
KW - Endothelium
KW - Isometric contraction
KW - Nitric oxide
KW - Rat aorta
UR - http://www.scopus.com/inward/record.url?scp=57149109120&partnerID=8YFLogxK
U2 - 10.1016/j.vph.2008.08.001
DO - 10.1016/j.vph.2008.08.001
M3 - Artículo
C2 - 18778795
SN - 1537-1891
VL - 50
SP - 14
EP - 19
JO - Vascular Pharmacology
JF - Vascular Pharmacology
IS - 1-2
ER -