Effect of an angiotensin-converting enzyme inhibitor on blood pressure and erythropoiesis in rats

Abstract

Positive correlation between systolic blood pressure and plasma renin substrate was demonstrated in Wistar-Kyoto rats when plasma renin substrate was reduced to within a range of 18 and 88% of control values with varying amounts of ramipril. When ramipril was given in amounts that had a maximum effect on systolic blood pressure, marked changes in erythropoietin, reticulocyte count and hematocrit % were observed. Consistent blood pressure-lowering effect was evident for several weeks after ramipril withdrawal. Furthermore, blood pressure obtained 3 days after the rats were taken off ramipril correlated positively with the hematocrit % measured while the rats were still on ramipril (r=0.83; P<0.001). Mean blood volume of 17 rats receiving ramipril was similar to that of the 10 control rats. Plasma and renal renin substrate were highly and positively correlated (r=0.86; P<0.001). Inasmuch as plasma renin substrate is rate-limiting for angiotensin I, it may reflect intrarenal AII and prove to be a useful clinical assessment of converting enzyme inhibition. The increased levels of renin, renin substrate and packed cell volume seen in rats fed Purina basal diet (10% fat) as compared with rats fed Purina lab chow (4.5% fat), support the working hypothesis that intrarenal angiotensin II controls both blood pressure and erythropoiesis.