To establish if the benefit of
angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect of the systemic hypotensive effect, we studied the effect of long-term
ramipril treatment on blood pressure, glomerular filtration rate, and urinary
protein excretion in
streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of
ramipril was prevented by a high
salt diet, which did not alter the degree of renal
angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking
solution. One week later, groups 2 and 3 received 0.4 mg/kg/day
ramipril in their drinking
solution, which was continued over a 2-month period.
Ramipril produced a blood pressure fall only in
water-drinking rats (group 3) despite a similar reduction in plasma and renal
angiotensin converting enzyme activity in groups 2 and 3.
Salt-loaded rats had a progressive increase in urinary
protein excretion over the duration of study.
Ramipril treatment prevented an increase in
protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular filtration rate was similar in all three groups.
Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on
proteinuria. Although it is possible that
angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic
proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit.