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

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 less than 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 less than 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.