Neuropeptide Y (NPY), a potent vasoconstrictor agent reported to be released, in addition to norepinephrine (NE), by sympathetic nerve endings during stress, may contribute to the pressor response to various stimuli. The objectives of this study were to determine (a) whether plasma NPY concentrations are altered during different types of stress (cold pressor test, mental stress, and active orthostatism) and (b) whether clonidine, via its central sympatholytic effect, affects the stress-induced blood pressure, NPY, and/or catecholamine changes. Eighteen untreated patients with mild essential or borderline hypertension participated in an acute randomized, double-blind, parallel study. The blood pressure and heart rate were recorded during three control periods, each followed by either a cold pressor test (CPT), a mental stress test (MS: mental arithmetic), or active orthostatism (AO), performed in a random order. Venous blood samples for catecholamines and NPY determination were taken at the end of each control and test period. This entire procedure was repeated after oral clonidine (150 micrograms) or placebo. Before treatment, a CPT, MS, or AO increased the blood pressure to the same extent. The stress-induced increase in plasma NE was greater during AO (+99 +/- 23%) than during CPT (+35 +/- 8%) and MS (+55 +/- 12%). The stress-induced increase in plasma epinephrine was only significant during MS (+142 +/- 69%). A small but significant increase in NPY (p < 0.05) was observed during AO only (+10 +/- 7%). Compared to placebo, clonidine significantly decreased the basal blood pressure and the pressor response to CPT, but did not change the pressor response to MS and AO.(ABSTRACT TRUNCATED AT 250 WORDS)