RESUMEN
Endothelial cells control the tone of the underlying smooth muscle by releasing relaxing factors, such as nitric oxide (NO), prostacycline, endothelium-derived hyperpolarizing factor (EDHF) and contracting factors such as thromboxane A2, endothelins, endoperoxides and superoxide anion. The term EDHF should be restricted to a relaxing factor(s) that differs from NO and prostacyclin. The nature of EDHF is as yet unknown. EDHF might be a cytochrome P-450 metabolite of arachidonic acid or an endogenous cannabinoid--anandamide. The EDHF component of the relaxation is more important in smaller than larger arteries. In various models of disease and in aging animals endothelium-dependent hyperpolarization is diminished. The identification of EDHF and the understanding of its physiological role could lead to the design of new therapies în several cardiovascular diseases.
Asunto(s)
Factores Biológicos/fisiología , Endotelio Vascular/fisiología , Animales , Ácido Araquidónico/metabolismo , Ácidos Araquidónicos/fisiología , Cannabinoides , Sistema Enzimático del Citocromo P-450/metabolismo , Endocannabinoides , Óxido Nítrico/fisiología , Alcamidas Poliinsaturadas , Vasodilatación/fisiologíaRESUMEN
Recent studies have described intracellular binding sites for angiotensine II. In vascular smooth muscle it was found that intracellular injection of angiotensin II increases the Ca2+ level. An alternative method for intracellular delivery of drugs is represented by using liposomes. Thus, the aim of this study was to characterize liposomes filled with angiotensinogen, angiotensine I (Ang I), angiotensine II (Ang II), and saralasin by a TLC method and examine the physiological effects of these on rat vascular smooth muscle. Ang II (for all concentrations tested in the aqueous phase) and Ang I (for concentrations less than 10(-4)M) did not affect the thin-layer chromatography migration of this type of vesicle, suggesting that dose-dependent effects on physio-pharmacological experiments could be studied. On the other hand, this type of experiment could not be performed for salarasin- or angiotensinogen-filled liposomes. Administration of liposomes containing Ang II (10(-6)M), Ang I (10(-6)M), angiotensinogen (10(-6)M) and saralasine (10(-6)M) caused the contraction to isolated rat aorta smooth muscle, suggesting the presence of active intracellular binding sites.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/análisis , Angiotensinas/análisis , Cromatografía en Capa Delgada/métodos , Saralasina/análisis , Angiotensina I/análisis , Angiotensina II/análisis , Angiotensinógeno/análisis , Animales , Liposomas/química , Masculino , Ratas , Ratas WistarRESUMEN
The thin-layer chromatographic (TLC) behaviour of small unilamellar liposomes containing inositol phosphates (IPs) was studied. The vesicles contained different concentrations of D-myo-inositol 1,4,5-triphosphate (IP3), D-myo-inositol 1,2,6-triphosphate (alpha-trinositol, PP 56, a novel Perstorp Pharma derivative), D-myo-inositol 1,3,4,5-tetraphosphate (IP4), D-myo-inositol 1,3,4,5,6-pentakisphosphate (IP5) and D-myo-inositol 1,2,3,4,5,6-hexakisphosphate (IP6). Migration of all liposome batches was compared to that of control liposomes (multilamellar and small unilamellar, both containing only triple-distilled water), and to that of free phosphatidylcholine (PC). The same amount of lipid was used in all situations. Thin-layer chromatography was performed with silica gel as adsorbent. The developing solvent was an n-buthanol:ethanol:water mixture in a 4:3:3 volume ratio. At doses higher than 10(-2) M liposomes containing alpha-trinositol and IP6 had a different migration than PC, MLV or SUV as well as all batches of liposomes. Physiological studies (using as model endothelized rat aorta rings) proved that in this situation they had no effects.