[Effects of propofol pretreatment on endothelin in oleic acid-induced acute lung injury]. / Efectos del pretratamiento con propofol sobre la endotelina en daño pulmonar agudo inducido por ácido oleico.

INTRODUCTION: Acute lung injury (ALI) is a pathological condition characterized by injury in the alveolar-capillary membrane that triggers local and systemic inflammation. Endothelin (ET) is a protein that regulates immune response and constricts blood vessels; when it is over-expressed, it may contribute to high blood pressure and lung injury. This work tries to determine if propofol may decrease hemodynamic, gasometric, microscopic, ET-1 plasmatic concentration, and immuno-histochemical alterations in an experimental model of oleic acid-induced acute lung injury. MATERIALS AND METHODS. Animals were classified into three groups (n = 6): group I was the control group; in group II, there was oleic acid-induced ALI with no treatment, and group III with propofol pre-treatment and oleic acid-induced ALI. RESULTS: All animals survived until the end of the study, and 100% of group II and group III developed ALI, with hemodynamic, gasometric and gravimetric alterations. However, group III showed less inflammatory infiltration and lower ET-1 expression in lung tissue. CONCLUSIONS: Pretreatment with propofol in a canine model of OA-induced ALI indicates that the drug has anti-inflammatory action, with a potential therapeutic role against progression of anti-inflammation and lung damage.

Hemodynamic and hormonal actions of adrenomedullin.

Adrenomedullin, a 52-amino acid residue peptide, has numerous biological actions which are of potential importance to cardiovascular homeostasis, growth and development of cardiovascular tissues and bone, prevention of infection, and regulation of body fluid and electrolyte balance. Studies in man using intravenous infusion of the peptide have demonstrated that, at plasma levels detected after myocardial infarction or in heart failure, adrenomedullin reduces arterial pressure, increases heart rate and cardiac output, and activates the sympathetic and renin-angiotensin systems but suppresses aldosterone. The thresholds for these responses differ, being lower under some experimental circumstances for arterial pressure than for the other biological effects. Adrenomedullin administration inhibits the pressor and aldosterone-stimulating action of angiotensin II in man. By contrast, the pressor effect of norepinephrine is little altered by concomitant adrenomedullin administration. Although in the absence of a safe, specific antagonist of the actions of endogenous adrenomedullin it is difficult to be certain about the physiological and pathophysiological importance of this peptide in man, current evidence suggests that it serves to protect against cardiovascular overload and injury. Hope has been expressed that adrenomedullin or an agonist specific for adrenomedullin receptors might find a place in the treatment of cardiovascular disorders.

Possíveis conexões entre hipertensäo e hipercolesterolemia, em relaçäo a aterosclerose: vias de inativaçäo do óxido nítrico e oxidação das lipoproteínas / Possible connections between hypertension and hypercholesterolemia in relation to atherosclerosis inactivation pathways of nitric oxide and lipoprotein

A disfunção endotelial tem um importante papel na patogênese de doenças cardiovasculares. Tem sido sugerido que o colesterol plasmático, particularmente o que está associado à LDL, é um dos principais fatores de risco para a aterosclerose. Contudo, a oxidação da LDL é um evento crucial na patogênese da aterosclerose. Além disso, a redução da biodisponibilidade do óxido nítrico (`ANTPOT. PONTO NOï) tem sido relacionada à disfunção endotelial presente na aterosclerose. A redução da bioatividade do `ANTPOT. PONTO NOï na hipercolesterolemia, na hipertensão e em outras desordens metabólicas associadas com a aterogênese parece ser multifatorial. Contudo, as alterações da produç/biodisponibilidade do `ANTPOT. PONTO NOï na hipercolesterolemia e na hipertensão é ainda controverso...

Effect of sodium chloride supplementation on urinary endothelin-1 excretion in premature infants.

We investigated the role of endothelin-1 in the renal adaptation to alterations in sodium balance in premature infants. The postnatal course of urinary endothelin-1 excretion, an estimate of renal endothelin-1 production, was compared in premature infants receiving low or high sodium intake. Sodium supplementation was given in a dose of 3 to 5 mmol/kg per day and 1.5 to 2.5 mmol/kg per day at the postnatal ages of 8 to 21 and 22 to 35 days, respectively. Sodium balance and urinary endothelin-1 excretion were determined weekly up to the fifth week of life. Urinary endothelin-1 concentration (expressed in picomoles per liter) and urinary endothelin-1 excretion (expressed either in terms of picomoles per square meter per day or picomoles per millimole creatinine) were significantly lower in infants receiving a high sodium intake compared with those receiving low sodium intake (p < 0.001) in weeks 2 through 5. We conclude that in sodium-depleted premature infants with high urinary sodium excretion, an angiotensin II-mediated increase in renal endothelin-1 production occurs, which acts in concert with angiotensin II to restore sodium balance.

Potent constrictor actions of endothelin-1, endothelin-2, and endothelin-3 in rat isolated portal vein.

In rings of rat portal vein, endothelin-1, endothelin-2, and endothelin-3 caused graded slow contractions and potentiated spontaneous contractions. The apparent EC50 values and maximal responses to 30 nM endothelin were 1.4 nM and 0.96 g for endothelin-1, 5.2 nM and 0.65 g for endothelin-2, and 1.7 nM and 0.62 g for endothelin-3 (n = 4-12). At concentrations producing half the contraction triggered by 80 mM KCl, the order of potencies was endothelin-1 greater than U46619 = angiotensin II greater than bradykinin greater than substance P greater than phenylephrine. Longitudinal portal-mesenteric vein preparations developed very modest contractions to endothelin-1 (0.13 g at 30 nM; n = 5), but their responses to 80 mM KCl and phenylephrine were greater than those of rings. Responses of rings to endothelin-1 were profoundly reduced in Ca(2+)-free medium, but less inhibition was obtained after incubation with nicardipine (up to 1 microM) and/or nickel (up to 0.5 mM), phorbol (up to 0.3 microM), staurosporine (up to 10 nM), or cromakalim (3 microM). Indomethacin (5.6 microM) did not affect responses to endothelin-1. Cromakalim (0.1-3 microM) also relaxed rings constricted with 0.3 nM endothelin-1, and this effect was partially reversed by glibenclamide (3 microM). Thus, endothelins, especially endothelin-1, are potent constrictors of portal vein rings but not of portal-mesenteric vein strips. Their action appears to rely largely on Ca2+ influx from the external medium (only in part via L- and T-type Ca2+ channels) and activation of protein kinase C but not on eicosanoid generation.(ABSTRACT TRUNCATED AT 250 WORDS)