RESUMEN
In fetal sheep, umbilical responsiveness to ANG II exceeds systemic vascular responsiveness. Fetal systemic vascular smooth muscle (VSM) exhibits an immature phenotype with decreased contractile protein contents, low 200-kDa myosin heavy chain (MHC) SM2, and significant nonmuscle MHC-B expression, whereas umbilical VSM phenotype is incompletely described. We tested the hypothesis that differences in vascular responsiveness could reflect dissimilarities in VSM phenotype. Actin, MHC, MHC isoforms, and active stresses were compared in strips of femoral arteries and aorta from near-term fetal (n = 12) and adult (n = 12) sheep to those in external and intra-abdominal umbilical arteries. Actin contents in fetal femoral artery and aorta were less (P = 0.006) than in external umbilical artery (7.37 +/- 1.4 and 7.53 +/- 0.7 vs. 21.6 +/- 2.2 microg/mg wet wt, respectively) as were MHC contents (3.17 +/- 0.4 and 2.84 +/- 0. 3 vs. 7.16 +/- 0.7, respectively). Whereas 204- and 200-kDa MHC were expressed equally in fetal systemic arteries, umbilical and adult arteries predominantly expressed the 204-kDa isoform (SM1); only fetal systemic VSM expressed MHC-B. Fetal systemic artery stresses and myosin light chain phosphorylation were less than those in umbilical and adult arteries (P < 0.001). Compared with umbilical and adult arteries, fetal systemic VSM is biochemically and functionally immature and thus umbilical VSM demonstrates precocious maturation resembling adult VSM in protein expression and function.
Asunto(s)
Arterias/metabolismo , Proteínas Musculares/metabolismo , Músculo Liso Vascular/metabolismo , Actinas/metabolismo , Animales , Aorta/embriología , Aorta/metabolismo , Arterias/embriología , Arteria Femoral/embriología , Arteria Femoral/metabolismo , Contracción Muscular , Músculo Liso Vascular/embriología , Cadenas Pesadas de Miosina/metabolismo , Cadenas Ligeras de Miosina/metabolismo , Fenotipo , Fosforilación , Ovinos , Arterias Umbilicales/embriología , Arterias Umbilicales/metabolismoRESUMEN
The effects of clinically used cardioactive agents in furazolidone-induced cardiomyopathy in the turkey poult have been recently reported, and note-worthy differences in cardioprotective efficacy of adrenergic effectors, calcium channel blockers, and cardiac glycosides have been noted in animal and human studies of heart failure. We therefore investigated the effects of chronic oral administration of cardioactive agents on ventricular tissue from normal turkey poults, and we determined whether these agents altered cardiac function, energetics, or transmembrane signaling pathways in a manner that might contribute to the varying degrees of cardioprotection and therapeutic efficacy reported previously. Creatine content was significantly higher in propranolol- and atenolol-treated animals. There was also higher lactate dehydrogenase and creatine kinase activities, reflecting an overall increase in energy reserve. Treatment with the calcium channel antagonists verapamil and nifedipine produced a significant increase in adenylyl cyclase activity and beta-adrenergic receptor density. Nifedipine treatment resulted in upregulation of both beta-adrenergic receptors and dihydropyridine receptors. This finding was associated with enhanced peak twitch force at all extracellular Ca2+ concentrations. We demonstrate for the first time that clinically used pharmacological agents (nifedipine and propranolol) result in alteration in two transmembrane signaling pathways, with associated alterations in physiological performance. Moreover, agents without cardioprotective effect in furazolidone-induced cardiomyopathy did not induce alterations in transmembrane signaling or energetics in normal hearts.