RESUMO
The effects of 1 nM ouabain (OUA) on the contractile actions of phenylephrine (PHE, 0.001-100 microg) and functional activity of the sodium pump (NKA) in isolated-perfused tail vascular beds from WKY and SHR were investigated. In preparations from SHR, perfusion with OUA in the presence of endothelium (E+) increased the sensitivity (pED50) of PHE (before: 2.14 +/- 0.06 versus after: 2.47 +/- 0.07; P < 0.05) without altering the maximal response (Emax). After endothelial damage, OUA reduced the Emax of PHE in SHR (before: 350 +/- 29 versus after: 293 +/- 25 mm Hg; P < 0.05). In SHR/E+, pretreatment with losartan (10 microM) or enalaprilat (1 microM) prevented the increased sensitivity to PHE induced by OUA. OUA increased NKA activity in SHR/E+ (before: 45 +/- 6 versus after: 58 +/- 5%, P < 0.05). Losartan (10 mg/Kg, i.v.) also abolished the increment in systolic and diastolic blood pressure induced by OUA (0.18 microg/Kg, i.v.) in anesthetized SHR. OUA did not alter the actions of PHE in either anesthetized WKY rats or vascular preparations. Results suggest that 1 nM OUA increased the vascular reactivity to PHE only in SHR/E+. This effect is mediated by OUA-induced activation of endothelial angiotensin converting enzyme that promotes the local formation of angiotensin II, which sensitizes the vascular smooth muscle to the actions of PHE.
Assuntos
Angiotensina II/metabolismo , Endotélio Vascular/metabolismo , Ouabaína/farmacocinética , Cauda/citologia , Angiotensina II/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Sinergismo Farmacológico , Quimioterapia Combinada , Enalaprilato/farmacologia , Glucose/administração & dosagem , Glucose/química , Hexametônio/farmacologia , Injeções Intravenosas , Losartan/antagonistas & inibidores , Losartan/farmacologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Ouabaína/administração & dosagem , Perfusão , Fenilefrina/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , ATPase Trocadora de Sódio-Potássio/fisiologia , Cauda/irrigação sanguínea , Cauda/metabolismo , Fatores de Tempo , Trometamina/administração & dosagem , Trometamina/química , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologiaRESUMO
Regenerating tail fins were studied in two species of teleosts, Tilapia rendalli and Cyprinus carpio, treated with indomethacin, aspirin, dexamethasone, penicillamine, and beta-aminoproprionitrile, drugs known to disrupt collagen metabolism in mammals. Collagen was studied under the light microscope by the Picrosirius-polarization method and also under the electron microscope. In general, these drugs disturbed the deposition and organization of collagen fibrils leading to abnormally thin or practically absent lepidotrichia and actinotrichia, and also to disorganized fibrous connective tissue. The resulting disorganization of the collagenous scaffolding of the regenerating dermoskeleton was probably responsible for a secondary effect on blastema distalization and on the general fin ray patterning that were also observed. The foregoing observations suggest that the stromal histoarchitecture of the regenerate plays a vital role in fin regeneration and indicate that these drugs may be useful in studying the extracellular matrix-cell interactions at the cellular and molecular level. In addition, the present findings provide a basis for developing different biological models by using teleost fin regeneration.