Angiotensin I, II, and III in sheep. A model of angiotensin production and metabolism.

The arterial and central venous concentrations of angiotensin I (AI), Val5-angiotensin II ([Val5]AII), and Val5-angiotensin III ([Val5]AIII(2-8)) were quantitatively determined in conscious sheep before and after sodium depletion. All three angiotensins were elevated in blood with progressive sodium loss. During sodium deficiency the arteriovenous concentration ratios (A:V) of AI, [Val5]AII, and [Val5]AIII(2-8) were found to be 0.48 +/- 0.03 (n = 9), 1.30 +/- 0.05 (n = 16), and 1.52 +/- 0.05 (n = 11) respectively. Intravenous infusion of [Val5]AII or [Val5]AIII(2-8) significantly elevated the A:V of respective angiotensins, being 2.09 +/- 0.28 (n = 5) for [Val5]AII and 2.2 +/- 0.37 (n = 6) for [Val5]AIII(2-8). The blood clearance rates of exogenous [Val5]AII and [Val5]AIII(2-8) in sodium-depleted sheep were calculated to be 135 +/- 15 liter/hr (n = 10) and 140 +/- 13 liter/hr (n = 10) respectively. Based on these experimental data, a steady-state model of angiotensin metabolism was constructed. If it is assumed that endogenous arterial blood [Val5]AII and [Val5]AIII(2-8) cleared metabolically at a similar rate as exogenous arterial blood angiotensins, it can be calculated that at steady-state 55% of the arterial [Val5]AII concentration was derived from the peripheral vascular bed. For [Val5]AIII(2-8), 63% of the arterial concentration was derived from the pulmonary circulation. The concentration of [Val5]AIII(2-8) in arterial blood was 42% of [Val5]AII.