RESUMEN
BACKGROUND: There is still considerable uncertainty regarding sensitivity of arterial blood pressure to endogenous peptides in renal hypertension. Many pathological processes including hypertension have been shown to be associated with release of endothelin-1 (ET-1). However the role of ET-1 in regulation of arterial blood pressure in hypertension is still controversial. OBJECTIVES: The role of endothelin-1 (ET-1) and angiotensin-II (AT-II) in malignant phase of renovascular hypertension has been assessed on the basis of arterial blood pressure increase and ETA receptor density measurements in Glodblatt-hypertensive rats (RVH). RESULTS: The arterial blood pressure response to sympatomimetic amines, vasopressors, the plasma ET-1 and AT-II levels as well as renal subtype-ETA receptor density were significantly increased in RVH rats with malignant hypertension. The dominance of vasopressor ETA receptors in RVH rats suggest the contribution of endothelin peptides to malignant renovascular hypertension. (Tab. 1, Fig. 7, Ref. 25.)
Asunto(s)
Acetilcolina/farmacología , Angiotensina II/sangre , Presión Sanguínea/efectos de los fármacos , Endotelina-1/sangre , Hipertensión Renovascular/fisiopatología , Norepinefrina/farmacología , Simpatomiméticos/farmacología , Vasoconstrictores/farmacología , Vasodilatadores/farmacología , Animales , Hipertensión Renovascular/sangre , Masculino , Ratas , Ratas WistarRESUMEN
Many physiological and pathological processes in the cardiac tissue have been shown to be associated with a release of endothelin (ET) peptides and with induction of specific ET-receptors and G-protein-coupled ion channels. However, the exact mechanism regulating ET-receptors in the myocardium is controversial. The response to ET-1, the most important member of the ET family, is rapidly attenuated by down-regulation of ET-receptors. The internalization of ET-1 bound to two subclasses of specific receptors (ET(A) and ET(B)) that are abundant in the myocardium has been hypothesized to activate and/or inhibit a variety of intracellular signal transducing systems. The [125I]ET-1, BQ-3020 and selective ET-antagonists were used to study the subtype-selective component of regulation of ET-1 receptors in myocardial membranes. We determined the characteristics of [125I]ET-1 binding and [3H]thymidine incorporation in whole cell saturation studies and measured Ca2+ channel induction and the total number of inactive Ca2+ channels in photoaffinity studies with [3H]azidopine. Here we demonstrate four important components of the complex ET-1 response in human, porcine and rat myocardium, leading to aberrant responses of cells. After ET-1 induction, adaptive subtype-ETB selective down-regulation predominated in human embryonic fibroblasts, in porcine membrane vesicles and in microsomal membranes of renal hypertensive rats, with preferential high affinity ET-1 binding to ETA receptors and with the resultant ETA mediated proliferative and mitogenic activation of human fibroblasts. The ET-1 induction was also accompanied by profound inactivation of Ca2+ channels in myocardial membranes.