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 (V-mca), 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 V-mca [-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 presser and adrenaline responses, but not the drop in V-mca, were significantly attenuated. 3. On tilting to 70 degrees the fall in V-mca 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 (0.1, 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 V-mca 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 V-mca and a rise in mean arterial pressure and adrenaline levels. The acute effects of caffeine on mean arterial pressure and adrenaline but not on V-mca are lost with sustained caffeine intake. These results suggest dissociation between the development of central and peripheral tolerance after chronic caffeine use.