Renal vascular and biochemical responses to systemic renin inhibition in dogs at low renal perfusion pressure

Renin is produced by the kidney and secreted into the systemic circulation. However, its biochemical and physiological role of regulating renal blood flow with changing renal perfusion pressure (RPP) is not fully understood. In this study, the function of the intrarenal renin for production of angio tensin (Ang) I and maintenance of vascular tone was evaluated in dogs under normal conditions and when the kidney was perfused at low RPP. The dog lef t kidney was perfused first at normal (100 mm Hg) and then at low (30 mm Hg ) RPP in the presence or absence of the renin inhibitor ciprokiren (3 mg/kg , i.v.). Both hemodynamic and biochemical parameters were measured. Lowerin g RPP markedly reduced left renal blood flow and elevated left renal vascul ar resistance. These effects were prevented by ciprokiren, which blocked th e intrarenal production of Ang I. Lowering RPP increased the renal venous/a rterial ratio from 1.4 +/- 0.1 to 3.6 +/- 0.3 for plasma renin activity and from 2.4 +/- 0.2 to 9.8 +/- 1.1 for Ang I, but did not change the venous/a rterial ratio for Ang II. The net renal venous conversion rate of Ang I to Ang II decreased from 0.22 to 0.09 after RPP was lowered, whereas the conve rsion rate in arterial blood was 1.35 and did not decrease significantly. O ur results demonstrated the importance of intrarenal renin-angiotensin syst em for Ang I production and for the maintenance of the vascular tone, espec ially at low RPP. Our study also shows the limited capacity for Ang I conve rsion in the renal vasculature in vivo.