HUMAN VASCULAR RENIN-ANGIOTENSIN SYSTEM AND ITS FUNCTIONAL-CHANGES INRELATION TO DIFFERENT SODIUM INTAKES

A growing body of evidence supports the existence of a tissue-based re nin-angiotensin system (RAS) in the vasculature, but the functional ca pacity of vascular RAS was not investigated in humans. In 28 normotens ive healthy control subjects, the metabolism of angiotensins through v ascular tissue was investigated in normal, low, and high sodium diets by the measurement of arterial-venous gradient of endogenous angiotens in (Ang I and Ang II ill two different vascular beds (forearm and leg) , combined with the study of I-125-Ang I and I-125-Ang II kinetics. In normal sodium diet subjects, forearm vascular tissue extracted 36+/-6 % of I-125-Ang I and 30+/-5% of I-125-Ang II and added 14.9+/-5.1 fmol . 100 mL(-1). min(-1) of de novo formed Ang I and 6.2+/-2.8 fmol . 10 0 mL(-1). min(-1) of Ang II to antecubital venous blood. Fractional co nversion of I-125-Ang I through forearm vascular tissue was about 12%. Low sodium diet increased (P<.01) plasma renin activity, whereas de n ovo Ang I and Ang II formation by forearm vascular tissue became undet ectable. Angiotensin degradation (33+/-7% for Ang I and 30+/-7% for An g II) was unchanged, and vascular fractional conversion of I-125-Ang I decreased from 12% to 6% (P<.01). In high sodium diet subjects, plasm a renin activity decreased, and de novo Ang I and Ang II formation by forearm vascular tissue increased to 22 and 14 fmol . 100 mL(-1). min( -1), respectively (P<.01). Angiotensin degradation did not significant ly change, whereas fractional conversion of I-125-Ang I increased from 12% to 20% (P<.01). Leg vascular tissue functional activities of RAS paralleled those of forearm vascular tissue both at baseline and durin g different sodium intake. These results provide consistent evidence f or the existence oi a functional tissue-based RAS in vascular tissue o f humans. The opposite changes of plasma renin activity and vascular a ngiotensin formation indicate that vascular RAS is independent from bu t related to circulating RAS.