The influence of hypertension and of treatment with the dihydropyridine-type Ca+2 antagonist nicardipine on peripheral nerve vasculature were investigated in spontaneously hypertensive rats (SHR). Male SHR were treated from the 16th to the 26th week of age with vehicle (control group), with nicardipine, at the hypotensive dose of 3 mg/kg/day, or at the nonhypotensive dose of 0.1 mg/kg/day or with an equihypotensive dose (10 mg/kg/day) of the nondihydropyridine-type vasodilator hydralazine. Age-matched normotensive Wistar-Kyoto (WKY) rats were left untreated and used as normotensive reference animals. In SHR a significant increase of systolic pressure values accompanied by sciatic nerve microvascular changes, involving primarily interfascicular arteries and to a lesser extent intrafascicular arteries, was observed. Treatment with the hypotensive dose of nicardipine countered hypertension-dependent microvascular changes occurring in both interfascicular and intrafascicular arteries. The nonhypotensive dose of nicardipine and hydralazine displayed a modest activity on interfascicular arteries, but significantly countered hypertension-related changes involving intrafascicular arteries. The above findings indicate the occurrence of hypertension-related changes of peripheral nerve microvasculature and of positive effects induced by appropriate pharmacological treatment. Further work is in progress to identify the functional relevance of microanatomical observations of the present study.