Angiotensin II blockade and the functions of the renin-angiotensin system

In anaesthetized dogs that were sodium-depleted or subjected to thoracic caval constriction, Sar1-Ala8-angiotensin II produced a striking decrease in aldosterone secretion; also, arterial pressure fell while plasma renin activity (PRA) increased. Recent preliminary observations in conscious dogs during angiotensin II blockade with measurements of the plasma aldosterone level, arterial pressure and PRA have confirmed these observations; a striking fall in plasma aldosterone and arterial pressure occurred while PRA increased. In the rat, sodium depletion produced a marked increase in PRA and aldosterone secretion; studies with angiotensin II blockade during administration of the nonapeptide converting enzyme inhibitor or Sar1-Ala8-angiotensin II demonstrated an important role for angiotensin II in mediating the increase in aldosterone secretion during sodium depletion in the rat. In experimental high output failure secondary to a large aortic-caval fistula, angiotensin II blockade revealed that angiotensin II decreases renal blood flow and helps to maintain the level of arterial pressure; thus, the kidney participates in the compensatory action of angiotensin II to increase total peripheral resistance. Angiotensin II blockade in both one and two-kidney renal hypertensive dogs revealed that angiotensin II was important in the pathogenesis of the acute phase, but in chronic renal hypertension the mechanisms appeared to be angiotensin II-dependent.