Effect of acute and chronic caffeine use on the cerebrovascular, cardiovascular and hormonal responses to orthostasis in healthy volunteers.

1. The effects of acute and chronic caffeine ingestion on supine- and tilt- (60 min at 70 degrees) induced changes in middle cerebral artery velocity (Vmca), heart rate, blood pressure and counter-regulatory hormone levels (catecholamines, growth hormone and cortisol) were studied in nine healthy volunteers. A double-blind, placebo-controlled design was used to study acute effects followed by an open study after 6 days of chronic caffeine use. 2. In the supine position, acute ingestion of caffeine (250 mg) was associated with a fall in Vmca [-11 cm/s, point estimate of difference versus placebo (95% confidence interval: -17, -6) cm/s, P < 0.001] and a rise in mean arterial pressure [+4 (1, 6) mmHg, P < 0.01] and plasma adrenaline levels [+138 (53, 223) pmol/l, P < 0.01]. After chronic caffeine use, the pressor and adrenaline responses, but not the drop in Vmca, were significantly attenuated. 3. On tilting to 70 degrees the fall in Vmca was greater with placebo than after acute caffeine ingestion [-10 (-14, -15) cm/s, P < 0.01], whereas increments (above supine values) in heart rate, mean arterial pressure and hormone levels were unchanged by caffeine. In contrast, the adrenaline [+126 (29, 282) pmol/l, P < 0.01] and noradrenaline [+0.6, 0.9) nmol/l, P < 0.05] responses to tilting were augmented after acute caffeine ingestion. Chronic caffeine supplementation did not alter the fall in Vmca associated with tilting, but significantly attenuated the adrenaline response (P < 0.01 compared with the acute study). 4. Acute caffeine ingestion and orthostasis are both associated with a reduction in Vmca and a rise in mean arterial pressure and adrenaline levels. The acute effects of caffeine on mean arterial pressure and adrenaline but not on Vmca are lost with sustained caffeine intake. These results suggest dissociation between the development of central and peripheral tolerance after chronic caffeine use.