Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1990 Oct;30(4):579–584. doi: 10.1111/j.1365-2125.1990.tb03816.x

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

J P McKaigue 1, D W Harron 1
PMCID: PMC1368248  PMID: 1981319

Abstract

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)

Full text

PDF
579

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Deering A. H., Riddell J. G., Harron D. W., Shanks R. G. Effect of acute and chronic indoramin administration on baroreflex function and tremor in humans. J Cardiovasc Pharmacol. 1988 Mar;11(3):284–290. doi: 10.1097/00005344-198803000-00004. [DOI] [PubMed] [Google Scholar]
  2. Deering A. H., Riddell J. G., Harron D. W., Shanks R. G. Effect of acute and chronic oral administration of alfuzosin on baroreflex function and tremor in man. Br J Clin Pharmacol. 1988 Apr;25(4):417–424. doi: 10.1111/j.1365-2125.1988.tb03324.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Goldman W. F., Saum W. R. A direct excitatory action of catecholamines on rat aortic baroreceptors in vitro. Circ Res. 1984 Jul;55(1):18–30. doi: 10.1161/01.res.55.1.18. [DOI] [PubMed] [Google Scholar]
  4. Govier W. C. A positive inotropic effect of phenylephrine mediated through alpha adrenergic receptors. Life Sci. 1967 Jul 1;6(13):1361–1365. doi: 10.1016/0024-3205(67)90182-8. [DOI] [PubMed] [Google Scholar]
  5. McAloney R., Mitchell H., Deering A. H., Shanks R. G., Harron D. W. Computerized evaluation of Valsalva's Maneuver before and during alpha-adrenoceptor blockade with alfuzosin. J Pharmacol Methods. 1987 Sep;18(2):163–177. doi: 10.1016/0160-5402(87)90009-x. [DOI] [PubMed] [Google Scholar]
  6. Morganti A., Sala C., Palermo A., Turolo L., Zanchetti A. Alpha 1-Adrenoceptor blockade: dissociation of its effects on renin release and arterial blood pressure in man. Clin Sci (Lond) 1981 Dec;61 (Suppl 7):307s–309s. doi: 10.1042/cs061307s. [DOI] [PubMed] [Google Scholar]
  7. Munch P. A., Brown A. M. Sympathetic modulation of rabbit aortic baroreceptors in vitro. Am J Physiol. 1987 Nov;253(5 Pt 2):H1106–H1111. doi: 10.1152/ajpheart.1987.253.5.H1106. [DOI] [PubMed] [Google Scholar]
  8. Munch P. A., Thoren P. N., Brown A. M. Dual effects of norepinephrine and mechanisms of baroreceptor stimulation. Circ Res. 1987 Sep;61(3):409–419. doi: 10.1161/01.res.61.3.409. [DOI] [PubMed] [Google Scholar]
  9. Sasso E. H., O'Connor D. T. Prazosin depression of baroreflex function in hypertensive man. Eur J Clin Pharmacol. 1982;22(1):7–14. doi: 10.1007/BF00606418. [DOI] [PubMed] [Google Scholar]
  10. Schümann H. J., Wagner J., Knorr A., Reidemeister J. C., Sadony V., Schramm G. Demonstration in human atrial preparations of alpha-adrenoceptors mediating positive inotropic effects. Naunyn Schmiedebergs Arch Pharmacol. 1978 May;302(3):333–336. doi: 10.1007/BF00508304. [DOI] [PubMed] [Google Scholar]
  11. Tomomatsu E., Nishi K. Increased activity of carotid sinus baroreceptors by sympathetic stimulation and norepinephrine. Am J Physiol. 1981 Apr;240(4):H650–H658. doi: 10.1152/ajpheart.1981.240.4.H650. [DOI] [PubMed] [Google Scholar]
  12. Uprichard A. G., Harron D. W., Wilson R., Shanks R. G. Effects of the myocardial-selective alpha 1-adrenoceptor antagonist UK-52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs. Br J Pharmacol. 1988 Dec;95(4):1241–1254. doi: 10.1111/j.1476-5381.1988.tb11761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wagner J., Schümann H. J., Knorr A., Rohm N., Reidemeister J. C. Stimulation by adrenaline and dopamine but not by noradrenaline of myocardial alpha-adrenoceptors mediating positive inotropic effects in human atrial preparations. Naunyn Schmiedebergs Arch Pharmacol. 1980 May;312(1):99–102. doi: 10.1007/BF00502581. [DOI] [PubMed] [Google Scholar]
  14. Wenzel D. G., Su J. L. Interactions between sympathomimetic amines and blocking agents on the rat ventricle strip. Arch Int Pharmacodyn Ther. 1966 Apr;160(2):379–389. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES