Effect of UK-52,046, an alpha 1-adrenoceptor antagonist, on baroreflex function in man

1. In a placebo controlled study (six healthy male subjects), the effects of UK-52,046 (0.4 microgram kg-1 i.v.) and prazosin (0.25 mg i.v.) on baroreflex function were compared, at doses which produced antagonism to phenylephrine, but which had no effect on supine blood pressure. 2. Baroreflex function [delta R-R interval ms mm Hg-1 change in SBP] was assessed following increases in systolic blood pressure (SBP) with phenylephrine and during the Valsalva manoeuvre. 3. At these doses neither UK-52,046 nor prazosin had an effect on supine SBP or heart rate; however following prazosin, standing SBPs at 5 s (69.7 +/- 7.6 mm Hg) and at 3 min (65.5 +/- 11.7 mm Hg) were less than the respective pre-treatment (P less than 0.05) values (96.0 +/- 2.9, 110.3 +/- 6.2 mm Hg) and placebo (82.7 +/- 5.6, 98.7 +/- 11.1 mm Hg). UK-52,046 had no significant effects on standing SBP at 5 s or 3 min. At 5 s, pre- and post-treatment R-R intervals (584 +/- 26, 541 +/- 27 ms respectively) were not significantly different with prazosin, but at 3 min the post-treatment R-R interval following prazosin (519 +/- 17 ms) was less (P less than 0.05) than the pre-treatment value (658 +/- 36 ms). 4. UK-52,046 had no effect on baroreflex sensitivity (12.7 +/- 1.3 ms mm Hg-1) compared with placebo (17.9 +/- 2.7 ms mm Hg-1).(ABSTRACT TRUNCATED AT 250 WORDS)