We have recently shown that treatment with the
calcium channel blocker nitrendipine may aggravate
albuminuria and glomerular injury in rats with two-kidney, one
clip renovascular hypertension if arterial blood pressure is not reduced. To test whether
nitrendipine also exerts its adverse renal effects when normotension is achieved, we examined the effect of combined
therapy with
nitrendipine and the converting
enzyme inhibitor enalapril on blood pressure,
albuminuria, glomerular filtration rate, and morphology of the nonclipped kidney. Rats treated with
enalapril alone or in combination with the
diuretic hydrochlorothiazide or rats treated with
nitrendipine alone served as controls.
Therapy was started 6 weeks after clipping of one renal artery.
Nitrendipine alone did not reduce blood pressure but significantly increased
albuminuria, diuresis, glomerular filtration rate, and glomerular volume and injury compared with untreated hypertensive controls. Increase of glomerular filtration rate, diuresis, and
albuminuria was reversible after withdrawal of
nitrendipine. Treatment with
enalapril alone decreased blood pressure significantly but not to normotensive levels and was without significant effect on
albuminuria and glomerular morphology. The combination of
nitrendipine and
enalapril reduced blood pressure to normotensive levels and not only prevented the increase of glomerular volume, glomerular filtration rate, diuresis, and
albuminuria caused by
nitrendipine alone but furthermore improved glomerular injury and
albuminuria to levels not significantly different from normotensive controls.
Enalapril in combination with the
diuretic had similar beneficial effects on blood pressure,
albuminuria, and glomerular injury. These data demonstrate that the adverse effects of
nitrendipine monotherapy on glomerular structure and function can be prevented by the combination of
nitrendipine and
enalapril when blood pressure is normalized.