Angiotensin II blockade in normal man: Interaction of renin and sodium in maintaining blood pressure

Angiotensin II blockade in normal man: Interaction of renin and sodium in maintaining blood pressure. Nine normotensive volunteers underwent six days of sodium-depletion followed by six days of sodium-repletion. On days six and twelve, the angiotensin II inhibitor, sar 1 -ala 8 -angiotensin II (saralasin), was infused i.v. and the blood pressure monitored with the subjects first in supine and then in upright position. The degree of induced sodium-depletion was varied over a considerable range in order to determine the level of sodium balance which is critical for maintaining blood pressure in the absence of the pressor action of angiotensin II. Five subjects had a cumulative sodium loss of more than 200mEq, mainly because of more vigorous diuretic treatment; upon infusion of saralasin, four exhibited marked hypotension in the erect position. The fifth became deeply hypotensive while still supine and was unable to stand up. Hypotension occurred in spite of clinical evidence of catecholamine oversecretion. In the four patients who had urinary sodium losses of less than 200 mEq, infusion of the inhibitor did not reduce their blood pressure. Following sodium-repletion, none of the nine subjects exhibited a blood pressure response to the inhibitor. These results suggest that angiotensin II plays an active role in sustaining normal blood pressure only under conditions of considerable sodium-depletion. Angiotensin II blockade in normal man: Interaction of renin and sodium in maintaining blood pressure. Nine normotensive volunteers underwent six days of sodium-depletion followed by six days of sodium-repletion. On days six and twelve, the angiotensin II inhibitor, sar 1 -ala 8 -angiotensin II (saralasin), was infused i.v. and the blood pressure monitored with the subjects first in supine and then in upright position. The degree of induced sodium-depletion was varied over a considerable range in order to determine the level of sodium balance which is critical for maintaining blood pressure in the absence of the pressor action of angiotensin II. Five subjects had a cumulative sodium loss of more than 200 mEq, mainly because of more vigorous diuretic treatment; upon infusion of saralasin, four exhibited marked hypotension in the erect position. The fifth became deeply hypotensive while still supine and was unable to stand up. Hypotension occurred in spite of clinical evidence of catecholamine oversecretion. In the four patients who had urinary sodium losses of less than 200 mEq, infusion of the inhibitor did not reduce their blood pressure. Following sodium-repletion, none of the nine subjects exhibited a blood pressure response to the inhibitor. These results suggest that angiotensin II plays an active role in sustaining normal blood pressure only under conditions of considerable sodium-depletion. Blocage de l'angiotensine II chez l'homme normal, interaction de la renine et du sodium dans le maintien de la pression arterielle. Neuf volontaires normotendus ont subi une depletion suivie d'une repletion sodee durant 2 periodes de six jours. Les sixiemes et douziemes jours l'inhibiteur de l'angiotensine II sar 1 -ala 8 angiotensine II (saralasin), a ete administre par voie intraveineuse, tandis que la pression arterielle etait enregistree, d'abord en position couchee puis en position debout. L'importance de la depletion sodee a ete variee en vue de definir le niveau critique necessaire au maintien de la pression arterielle en l'absence d'activite pressive de l'angiotensine II. Cinq sujets ont eu une perte cumulee de sodium de plus de 200 mEq, principalement en raison d'un traitement diuretique plus important. Lors de la perfusion de saralasin quarte d'entre eux ont developpe une hypotension importante en orthostatisme, le cinquieme a presente un chute tensionnelle grave en position couchee deja, rendant impossible toute station debout. L'hypotension est survenue malgre des signes cliniques de secretion accrue de catecholamines. Chez les quatre sujets dont la perte de sodium a ete inferieure a 200mEq l'inhibiteur n'a pas entraine de modification tensionnelle. Apres repletion sodee, aucun des neuf sujets n'a presente de modification de pression en reponse a l'inhibiteur. Ces resultats suggerent que l'angiotensine II ne joue un role actif dans le maintien d'une pression arterielle normale que dans des conditions de depletion sodique importante.