Angiotensin-Ii Blockade in Man by Sar1-Ala8-Angiotensin Ii for Understanding and Treatment of High Blood-Pressure

Angiotensin II, aldosterone and arterial pressure: a quantitative approach. Arthur C. Corcoran Memorial Lecture.

“…Thus McCaa 169 in the dog, and Noth and colleagues 1 " in man, did not see a consistent fall in plasma aldosterone when saralasin was given in sodium depletion, and considered the agonist effect as a possible explanation. By contrast, however, Stephens et al 18 * did obtain a significant reduction in plasma aldosterone by administering saralasin to sodium-deficient dogs.…”

Blockade of the renin-angiotensin system for renal future perspectives protection: from history to future perspective

“…With these agents, Brunner and Gavras again demonstrated that BP control was achievable with a combination of a RAS blocker and salt depletion using furosemide. 5,6 When captopril became available in the late 70's, 7 the same authors demonstrated that BP of hypertensive patients with chronic renal failure who were resistant to all previous therapies, could be normalised with the administration of captopril and furosemide. 8 At a time when severe hypertension was still treated with bilateral nephrectomy.…”

Clinical efficacy and tolerability of candesartan cilexetil

“…Ang II analogue peptides such as saralasin (Sar, 1 Ala 8 -Ang II) or sarile (Sar, 1 Ile 8 -Ang II) have been developed and used clinically for the detection of angiotensinogenic hypertension. [1][2][3] However, these peptides have not been used extensively because administration is limited to intravenous injection.…”

“…After the synthesis of these compounds, Timmermans et al 5 discovered DuP 753 (losartan), a potent orally active, nonpeptide Ang II receptor antagonist. 5 Candesartan cilexetil is a highly potent and longlasting AT 1 developed in Japan. 6,7 Candesartan cilexetil is a prodrug; the active metabolite is candesartan, which is predominantly excreted into the faeces via bile.…”