Renal adaptive mechanisms in aged and hypertensive humans: possible effects of treatment

In the aging kidney renal blood flow and glomerular filtration rate are reduced due to glomerulosclerosis. On this regard, hypertension has synergistic effects and may lead to end-stage renal disease in a significant proportion of cases.

To study the effects of antihypertensive drugs in an acute setting, we expressly designed an acute experiment to assess the renal response to mental stress (MS). In healthy elderly, the response was characterized by a prolonged and pronounced renal vasoconstriction, due to a reduction in renal autacoid modulatory capacity, particularly of prostaglandins. In older patients with isolated systolic hypertension, the response to MS was impaired, being characterized by a passive vasodilation with hyperfiltration. The effects of antihypertensive drugs were evaluated twice in adults patients with mild to moderate essential hypertension: after two weeks of pharmacological wash-out and after two weeks of treatment with the ACE-inhibitor trandolapril (4 mg), or the non-dihydropyridinic Ca2+ channel blocker verapamil (240 mg), or both (2 mg + 180 mg).

While the three antihypertensive regimens reduced blood pressure to a similar extent, their effects on the renal response to MS were different. Each regimen re-established a renal vasoconstrictive response to adrenergic activation. However, with trandolapril, renal vasoconstriction was limited, as it occurs physiologically, to the period of blood pressure rise, while verapamil, or the combination of the two drugs, were associated with more prolonged vasoconstriction.

Further studies are needed to confirm the nephroprotective effects of these drugs, particularly of ACE-inhibitors. These data may be a pathophysiological basis for future clinical trials.