CONVERTING-ENZYME INHIBITION AND RENAL TISSUE ANGIOTENSIN-II IN THE RAT

Multiple observations suggest local control of renal function via an intrarenal renin-angiotensin system, including evidence for local angiotensin (Ang) II production. Our first goal was to examine renal tissue Ang I:Ang II relations to ascertain whether Ang II formation differs in the circulation and in renal tissue. We have recently shown an authentic Ang II/Ang I ratio of 1.5:1 in renal lymph, the opposite of the Ang II:Ang I relation in plasma. Our second goal was to examine the influence of maximal angiotensin converting enzyme inhibition on these relations in plasma and in renal tissue. We used two converting enzyme inhibitors with differing lipid solubility, on the premise that tissue penetration and action might differ on that basis. We measured Ang I and Ang II in plasma and renal tissue of rats given an intravenous dose of either vehicle, enalapril, or ramipril, over a wide dose range, from 0.1 to 10.0 mg/kg IV. Renal and plasma angiotensin concentrations were measured by high-performance liquid chromatography and radioimmunoassay. Whereas the Ang I concentration in normal rat plasma (273+/-84 fmol/mL) was over threefold the plasma Ang II concentration (83+/-12 fmol/mL), the ratio was reversed in the kidney (Ang II, 178+/-12 versus Ang I, 91+/-3 fmol/g; P<.001). Although ramipril and enalapril induced an indistinguishable dose-related acute fall in blood pressure and plasma Ang II concentration, lower enalapril doses were less effective in reducing renal tissue Ang I:Ang II conversion and Ang II concentration (P<.025). The results confirm differences in the intrarenal and plasma compartments for Ang I and Ang II, compatible with different patterns of Ang II generation and suggest that converting enzyme inhibitors differ in their ability to reach and act in a large intrarenal compartment, but their maximal influence leaves substantial authentic Ang II generation.