title: Inhibition of PKC-dependent extracellular Ca2+ entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas.
abstract: We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF, México.
authors.forename: J
authors.initials: J
authors.lastname: Padilla
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF, México.
authors.forename: R M
authors.initials: RM
authors.lastname: López
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF, México.
authors.forename: P
authors.initials: P
authors.lastname: López
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF, México.
authors.forename: M C
authors.initials: MC
authors.lastname: Castillo
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF, México.
authors.forename: E
authors.initials: E
authors.lastname: Querejeta
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF, México.
authors.forename: A
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF, México.
authors.forename: E F
authors.initials: EF
authors.lastname: Castillo
mesh_terms: D000803:Angiotensin I / Q000032:analysis; D000804:Angiotensin II / Q000032:analysis; D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries / Q000503:physiopathology* / Q000601:surgery; D001017:Aortic Coarctation / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000293:injuries / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011863:Radioimmunoassay; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D009467:Neuromuscular Depolarizing Agents; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D010656:Phenylephrine; D000803:Angiotensin I; D011493:Protein Kinase C; D011188:Potassium; D002118:Calcium
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