Pressure–natriuretic and hemodynamic adjustments to chronic ACE inhibition in inbred F344 and Lewis rat strains

Abstract

Genetic background has a major influence on the severity of renovascular disease. Previously we showed that Lewis rats with inducible hypertension caused by transgenic renin expression have lower blood pressure, higher renal plasma flow (RPF) and glomerular filtration rate (GFR) and are relatively protected from hypertensive renal microvascular injury compared to Fisher (F344) rats. Using a congenic/consomic approach we determined that a polymorphism of the angiotensin converting enzyme (ACE) gene is a major contributory factor in explaining these strain differences.In the current study we have compared renal function in anaesthetised, non transgenic F344 and Lewis rats. Pressure‐natriuresis (PN) and pressure‐renal blood flow (PRBF) relationships were measured in groups of rats pre‐treated with and without Captopril (80mg/L drinking water 1–2wks) to inhibit ACE activity. Control F344 rats had higher baseline blood pressure and poorer PN compared with Lewis (ie shallower slope of PN curve). Captopril treatment significantly improved RBF without affecting PN in F344 rats. Conversely, Captopril reduced the slope of the PN curve in Lewis rats without affecting RBF responses to pressure. Taken together these results indicate a dominant vascular response to ACE inhibition in F344 compared with a dominant tubular response in Lewis rats.