In the present study we investigated the effect of a single dose, and 3 months of treatment with
spirapril on kidney function, renin-angiotensin system, renal handling of
sodium and blood pressure, in patients with reduced kidney function (serum
creatinine 1.5-3 mg%) and
hypertension. A single dose of 6 mg
spirapril given at the beginning of the study did not affect glomerular filtration rate (GFR), renal plasma flow (RPF),
angiotensin converting enzyme (ACE) activity, plasma
renin activity (PRA) or renal handling of
sodium. When the single dose of
spirapril was given after 3 months of treatment with this agent, renal hemodynamics and PRA did not change. ACE activity, which was depressed by the previous
spirapril treatment, decreased further (from 9.5 +/- 3.1 to 1.4 +/- 1.0 nmol/ml/min), (p < 0.05). Administration of 6 mg
spirapril o.d. for 3 months did not have any effect on GFR or RPF. Serum ACE activity decreased from 92.1 +/- 8.0 to 5.1 +/- 2.6 nmol/ml/min (p < 0.05) and PRA increased from 1.4 +/- 1.2 to 4.1 +/- 3.6 ng/ml/min (p < 0.05). Plasma
aldosterone did not change. Similar results were obtained when
spirapril was combined with 5 mg
isradipine in the initial and final single dose, or in the 3 months' treatment (5 mg o.d.). Blood pressure was normalized in 38% of the patients who received
spirapril and in 71% of the patients who received
spirapril and
isradipine. Thus, (a) treatment with
spirapril in patients with mild to moderate
chronic renal insufficiency was not associated with deleterious effects on kidney function; (b)
spirapril in a dose of 6 mg alone or in combination with 5 mg
isradipine is effective in reducing blood pressure in hypertensive patients with reduced kidney function.