Human Vascular Renin-Angiotensin System and Its Functional Changes in Relation to Different Sodium Intakes

Abstract

A growing body of evidence supports the existence of a tissue-based renin-angiotensin system (RAS) in the vasculature, but the functional capacity of vascular RAS was not investigated in humans. In 28 normotensive healthy control subjects, the metabolism of angiotensins through vascular tissue was investigated in normal, low, and high sodium diets by the measurement of arterial-venous gradient of endogenous angiotensin (Ang) I and Ang II in two different vascular beds (forearm and leg), combined with the study of 125I-Ang I and 125I-Ang II kinetics. In normal sodium diet subjects, forearm vascular tissue extracted 36+/-6% of 125I-Ang I and 30+/-5% of 125I-Ang II and added 14.9+/-5.1 fmol x 100 mL(-1) x min(-1) of de novo formed Ang I and 6.2+/-2.8 fmol x 100 mL(-1) x min(-1) of Ang II to antecubital venous blood. Fractional conversion of 125I-Ang I through forearm vascular tissue was about 12%. Low sodium diet increased (P<.01) plasma renin activity, whereas de novo Ang I and Ang II formation by forearm vascular tissue became undetectable. Angiotensin degradation (33+/-7% for Ang I and 30+/-7% for Ang II) was unchanged, and vascular fractional conversion of 125I-Ang I decreased from 12% to 6% (P<.01). In high sodium diet subjects, plasma renin activity decreased, and de novo Ang I and Ang II formation by forearm vascular tissue increased to 22 and 14 fmol x 100 mL(-1) x min(-1), respectively (P<.01). Angiotensin degradation did not significantly change, whereas fractional conversion of 125I-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 during different sodium intake. These results provide consistent evidence for the existence of a functional tissue-based RAS in vascular tissue of humans. The opposite changes of plasma renin activity and vascular angiotensin formation indicate that vascular RAS is independent from but related to circulating RAS.

Plasma Vitamin D Level and Change in Albuminuria and eGFR According to Sodium Intake

“…Preclinical studies have shown that high sodium intake increases several components of the intrarenal RAAS, including angiotensinogen (12), ACE activity (34), and Ang II (35). Accordingly, in humans, high sodium intake increased the peripheral vascular conversion of Ang I to Ang II, indicating an increase in tissue ACE activity (36). Increased renal ACE activity caused by high sodium intake combined with increased renin production caused by low vitamin D (24,37) may concertedly promote progression of albuminuria.…”

The influence of the ACE (I/D) polymorphism on systemic and renal vascular responses to angiotensins in normotensive, normoalbuminuric Type 1 diabetes mellitus

“…On multivariate analysis we found that sodium intake also modified the effect of ACE genotype on AngI response, independent from AngII response. The mechanism underlying this interaction between sodium status, ACE genotype and AngI responsiveness may be related to effects of sodium status on tissue AngI conversion [28]. However, genotype-associated effects of differences in baseline values during the different sodium intakes might also be involved.…”

Management of High Blood Pressure in Blacks

“…26,[87][88][89] However, the majority of blacks with HTN do not have fully suppressed circulating renin levels, 90 and dietary salt-induced suppression of renin production and, thereby, circulating renin levels have been associated with higher, not lower, levels of vascular angiotensin II production. 91 Several reports have highlighted the significant overlap in BP responses of blacks and whites to monotherapy with ACE inhibitors and the finding that the variation of BP response is much larger within racial/ethnic groups than between them. 87,88 In addition, other studies of blacks and whites have suggested greater, not lesser, activation of the renal RAS in healthy blacks, 92 as well as a blunted suppression of intrarenal RAS activity in blacks compared with whites when consuming a high-sodium diet.…”

“…93 This observation might also help explain why the largest racial differences in BP response during RAS blockade occur in the setting of a high dietary sodium intake; dietary sodium intake in salt-sensitive humans suppresses urinary NO metabolites 94,95 and augments vascular angiotensin II production. 91 Furthermore, the excessive rates of pressure-related target-organ injury in blacks with HTN (LVH, CKD, and proteinuria), as well as the high rates of obesity, have all been linked to RAS activation.…”