Papel de la agiotensina II en el desarrollo aterosclerótico: efecto de su bloqueo / Role of angiotensin II in the development of atherosclerosis: effect of blockade

La angiotensina II, el principal efector del sistema renina-angiotensina, ejerce un papel importante en la génesis y en las complicaciones de la aterosclerosis. La angiotensina II estimula la producción de especies reactivas de oxígeno en el vaso que desempeñan un papel clave en la disfunción endotelial y en la oxidación de las lipoproteínas de baja densidad (LDL). Asimismo, este péptido participa en la inducción de la respuesta inflamatoria en la pared vascular mediante la producción de moléculas de adhesión y citoquinas quimiotácticas y proinflamatorias. La angiotensina II, además, estimula la proliferación y migración de células de músculo liso y modula el cambio fenotípico de las mismas dando lugar a un aumento de la síntesis de la matriz extracelular. Finalmente, la angiotensina II también participa en las complicaciones de la aterosclerosis al favorecer la ruptura de la placa y trombogenicidad de la misma. En consecuencia, el sistema renina-angiotensina desempeña un papel clave en la patofisiología de la aterosclerosis, por lo que su bloqueo ejercerá un efecto beneficioso sobre el desarrollo aterosclerótico previniendo las alteraciones trombóticas asociadas a él (AU)

(1-Sar, 8-Ile) angiotensin II in the treatment of inhalation injury: a pilot study.

The patients were three men and two women with moderate to severe inhalation injury. Each patient received immediate fluid therapy and all required intubation for respiratory management. At some time between 24 and 72 hours after the injury, the synthetic angiotensin analogue (1-Sar, 8-Ile) angiotensin II was infused at a rate of 100 ng/kg/min for 10 minutes, 200 ng/kg/min for another 10 minutes, and 300 ng/kg/min for 30 minutes. The mean (+/- SD) PaO2 increased from 80.8 +/- 26.9 mmHg before to 89.8 +/- 27.3 mmHg after the infusion (P < 0.05) and the PaCO2 decreased from 42.4 +/- 8.3 to 39.6 +/- 7.9 mmHg (P < 0.05). A transient pressor response was noted in all patients. The results suggest that this angiotensin II analogue may be of benefit in the treatment of inhalation injury and other types of acute lung injury.

Evaluation of (1-sarcosine, 8-isoleucine) angiotensin II as a therapeutic agent for oleic acid-induced pulmonary edema.

(1-Sarcosine, 8-isoleucine) angiotensin II was assessed as a therapeutic agent for acute respiratory distress syndrome with oleic acid pulmonary edema in sheep used as an experimental model. Under general anesthesia with controlled mechanical ventilation with 100% oxygen, 32 sheep received oleic acid (0.075 ml/kg) intravenously. After oleic acid infusion, 20 animals were treated with continuous intravenous infusion of the angiotensin II analogue; nine received 300 ng/kg/min, six received 600 ng/kg/min, and five received 2000 ng/kg/min. Cardiopulmonary measurements were repeated every 30 minutes for 270 minutes. According to time-integrated PaO2, six of 15 animals of the groups given 300 and 600 ng/kg/min (43%) did not respond to the treatment. All animals responded in the group given 2000 ng/kg/min. Animals in the latter group had lower Qs/Qt, PaCO2, and airway resistance than had the control animals. Elevation of pulmonary vascular resistance was limited and mean arterial blood pressure was well maintained. These results reveal that (1-Sar, 8-Ile) angiotensin II is effective in the treatment of oleic acid-induced pulmonary edema.

A case of hyperreninemic hypertension with unilateral hydronephrosis.

A patient with unilateral ureteral obstruction by urolithiasis at the ureteropelvic junction was accompanied by hypertension. Plasma renin activity (PRA) was high in peripheral veins and was significantly higher in the renal vein drained from the affected kidney than the contralateral. Infusion of angiotensin II antagonist or an oral administration of captopril, an angiotensin converting enzyme (ACE) inhibitor, resulted in a prompt drop of blood pressure. After pyelolithotomy was successfully performed, both the blood pressure and peripheral PRA completely normalized. It is suggested that the renin-angiotensin system might have played a major role in the mechanism of the accompanied hypertension. Hyperreninemia could have been caused by both renal ischemic vasoconstriction, which might be due to uretero-renal reflex, and increased synthesis of prostaglandins resulting from ureteropelvic obstruction.

Effect of indomethacin on responses to [sar-ileu]-angiotensin II.

The role of prostaglandins in immediate and sustained pressor responses to [sar-ileu]-angiotensin II was studied, using indomethacin, in 12 patients with essential hypertension. Blood pressure rose within 1 to 2 min, peaked in 4 to 8 min, then fell gradually, but did not return to the baseline level, at the end of 30-min infusion period of the angiotensin II analogue. After 2 days on indomethacin, both immediate and sustained diastolic pressure responses to the analogue (both, P less than 0.01) rose when the basal plasma renin activity (PRA) fell (P less than 0.05); this was associated with 56% suppression of urinary prostaglandin E excretion. Both the immediate and late phases of blood pressure response may be affected by indomethacin, probably not only because of greater availability of angiotensin receptors due to decrease endogenous angiotensin, but also because of alteration of end-organ sensitivity to angiotensin II through inhibition of prostaglandin synthesis. This speculation is supported by the difference in slopes of the regression line relating change in diastolic blood pressure to basal PRA, indicating that there is less effect on controls for a given PRA level than on treated subjects.

The sustained antihypertensive effect of chronic cerebroventricular infusion of angiotensin antagonist in spontaneously hypertensive rats.

The angiotensin antagonist [Sar1-Ile8]angiotensin II was infused into the lateral ventricles of mature spontaneously hypertensive and normotensive Wistar-Kyoto rats. Infusions were maintained at rats of 1200 ng/h for 6 days, and blood pressure was measured daily in the unanesthetized state. Blood pressure reduction occurred promptly and only in the hypertensive animals. This antihypertensive effect persisted for several days after discontinuation of the infusion. In contrast, iv infusion of the angiotensin antagonist at comparable doses failed to alter blood pressure in any significant fashion. These data suggest that the brain isorenin system participates in the maintenance of hypertension in the spontaneously hypertensive rat.