Renal protection with calcium antagonism in essential hypertension

The natural history of uncontrolled essential hypertension, with respect to renal function, is characterized by a progressive rise in renal vascular resistance, a progressive fall in effective renal plasma flow, and a progressive fall in glomerular filtration rate. Sustained effective antihypertensive therapy may reverse this pathophysiological sequence, preventing the development of arteriolar nephrosclerosis. It is unknown whether such a therapeutic benefit is a nonspecific response to controlling systemic hypertension, or is dependent on controlling both systemic and glomerular hypertension. Recent experimental evidence indicates that the control of systemic blood pressure may not necessarily be associated with control of glomerular capillary hypertension. The renal effects of calcium antagonists in essential hypertensive patients are only now being characterized. We have demonstrated that diltiazem, amlodipine, and nifedipine monotherapies enhance glomerular filtration rate and effective renal plasma flow, and lower renal vascular resistance. Although calcium antagonists attenuate the intrarenal effects of norepinephrine and angiotensin II, the precise mechanism(s) by which these drugs reverse the functional renal abnormalities in the essential hypertensive state, and by which they may attenuate the progression of hypertensive renal disease, are unknown. It is our hypothesis that renal protection requires normalization of both systemic and glomerular capillary pressure. Calcium antagonists have the ability to control systemic hypertension. If they can be demonstrated experimentally to reduce both pre- and post-glomerular capillary resistances (i.e. maintain a normal glomerular capillary pressure), they can be expected to provide long-term renal protection.