The effects of increasing oral doses of caffeine (45, 90, 180 and 360 mg) on effective renal plasma flow (ERPF), plasma renin activity (PRA), serum electrolytes, plasma noradrenaline, blood pressure and heart rate were studied in eight healthy male volunteers. Urine volume was increased by 360 mg of caffeine only. At caffeine doses greater than 90 mg urinary sodium excretion was significantly increased. There were no changes in ERPF. Serum potassium was significantly reduced by 360 mg of caffeine. Caffeine increased systolic pressure in a dose related manner. Diastolic pressure was also increased, but not in relation to dose. A 360 mg dose of caffeine produced a late increase in heart rate. These changes were not associated with any alterations in PRA or in plasma noradrenaline.

1 The acute peripheral vascular and diuretic effects of intravenous frusemide 10 mg and 20 mg were compared with those of bumetanide 250 pug and 500 ,ug in a group of 10 salt depleted volunteers. 2 Significant reductions in forearm blood flow (FBF) were observed after frusemide 10 mg (-0.77 ml 100 ml-' min-' P < 0.05) and 20 mg (-0.75 ml 100 m11 minil P < 0.01 at 15 min). No changes were observed after bumetanide. The reductions in blood flow produced by frusemide were significantly different from those of bumetanide (P < 0.05) at 15 min. 3 Increases in venous capacitance (VC) and mean arterial blood pressure (MAP) were observed after frusemide but these differences were not statistically different from placebo or bumetanide. No increases were seen after bumetanide. 4 Plasma aldosterone concentrations were unchanged after either drug but plasma renin activity (PRA) was increased after frusemide 10 mg (4.42 + 1.01 -+ 8.50 + 1.90 ng A I ml-' h'1 P < 0.01) and 20 mg (4.01 ± 0.72 --7.81 ± 2.27 ng A I m[71 h-1 P < 0.05). No increases were observed after bumetanide and significant differences between bumetanide and frusemide were observed (P < 0.01). 5 This study demonstrates that the acute peripheral arterial effects of frusemide are not observed after comparable diuretic doses of bumetanide. The differences appear to be related to the ability of the drugs to stimulate acute renin release from the kidney.

No abstract

Adrenergic receptors (alpha 2, beta 2), plasma noradrenaline, heart rate and the pressor responsiveness to infused noradrenaline were examined in ten healthy male volunteers before and after 2 weeks of placebo or captopril therapy in a double blind cross-over study. No significant differences in these measurements were observed between the captopril and placebo treated groups. The study shows that in sodium replete normotensive subjects, long-term angiotensin converting enzyme inhibition does not lead to changes in adrenoceptor density. There is also no alteration in plasma noradrenaline levels nor in the pressor responsiveness to infused noradrenaline. These data suggest that the known interaction between the renin-angiotensin system and the sympathetic nervous system observed in animals is probably of little significance in man.

1 The effect of captopril 12.5 mg three times daily for 14 days on baroreflex sensitivity was investigated in six normotensive salt-replete male subjects. 2 Baroreflex sensitivity [A/R-R interval ms/mmHg systolic blood pressure (SBP)] was assessed following decreases and increases in SBP with glyceryl trinitrate and phenylephrine respectively and during Valsalva's manoeuvre. 3 Captopril had no effect on supine intra-arterial SBP or R-R interval on days 1 and 15 compared with placebo. However decreases (P < 0.05) which occurred in plasma angiotensin II on day 1 (12.3 ± 0.8 to 7.6 ± 1.5 pg ml-') and on day 15 (14.5 ± 1.5 to 6.3 + 0.5 pg ml-1) and increases (P < 0.02) in plasma renin activity on day 1 (1.2 ± 0.7 to 4.8 ± 0.8 ng A I ml-1 h-1) and on day 15 (1.1 ± 0.2 to 5.4 ± 0.9 ng A I ml-h'-) compared with placebo, indicated angiotensin-converting enzyme inhibition. 4 Baroreflex sensitivity was unchanged by captopril on day 1 and day 15 compared with placebo following the use of glyceryl trinitrate and phenylephrine to deactivate and activate respectively the baroreceptors, and during the strain and release phases of Valsalva's manoeuvre.