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. 1989 Jul;97(3):941–949. doi: 10.1111/j.1476-5381.1989.tb12035.x

Phentolamine and structurally related compounds selectively antagonize the vascular actions of the K+ channel opener, cromromakalim.

G A McPherson 1, J A Angus 1
PMCID: PMC1854571  PMID: 2758244

Abstract

1. The effects of cromakalim, a novel vasodilator agent believed to open K+ channels, were studied in a range of large and small arteries in vitro. In dog isolated coronary artery, precontracted with U46619 (a thromboxane A2-mimetic), cromakalim caused concentration-dependent relaxation which could be inhibited by phentolamine (10-100 microM). 2. The ability of phentolamine to antagonize cromakalim was selective since it did not affect responses to a number of other vasodilators including isoprenaline, nitroprusside or nicorandil. 3. The effect of phentolamine was not related to its alpha-adrenoceptor blocking actions since other alpha-adrenoceptor antagonists (prazosin 10 microM, rauwolscine 10 microM and phenoxybenzamine 1 microM) failed to influence the action of cromakalim. 4. A number of compounds structurally related to phentolamine were also able to block the vaso-relaxant response to cromakalim in the dog isolated coronary artery. The rank order of potency was alinidine = phentolamine = ST91 greater than tramazoline = naphazoline. Clonidine and tolazoline were inactive. The most potent compounds (alinidine and phentolamine) were effective only at concentrations above 1 microM. 5. Electrophysiological studies, in which resting membrane potential and tension were measured simultaneously, were carried out on rat isolated femoral artery. Phentolamine (30 microM) antagonized both the vasorelaxation and hyperpolarization caused by cromakalim. 6. These results suggest that phentolamine and some structurally related compounds, may inhibit K+ channel opening, an action which would account for their ability to antagonize the actions of cromakalim. Such compounds may prove useful in determining the role of K+ channels in regulating vascular smooth muscle tone in vivo and in vitro.

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Selected References

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  1. Allen S. L., Boyle J. P., Cortijo J., Foster R. W., Morgan G. P., Small R. C. Electrical and mechanical effects of BRL34915 in guinea-pig isolated trachealis. Br J Pharmacol. 1986 Oct;89(2):395–405. doi: 10.1111/j.1476-5381.1986.tb10273.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angus J. A., Broughton A., Mulvany M. J. Role of alpha-adrenoceptors in constrictor responses of rat, guinea-pig and rabbit small arteries to neural activation. J Physiol. 1988 Sep;403:495–510. doi: 10.1113/jphysiol.1988.sp017260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coldwell M. C., Howlett D. R. Specificity of action of the novel antihypertensive agent, BRL 34915, as a potassium channel activator. Comparison with nicorandil. Biochem Pharmacol. 1987 Nov 1;36(21):3663–3669. doi: 10.1016/0006-2952(87)90017-7. [DOI] [PubMed] [Google Scholar]
  4. Digges K. G., McPherson G. A., Summers R. J. Pharmacological investigation of alpha-adrenoreceptors in guinea-pig splenic capsule. J Auton Pharmacol. 1981 Sep;1(4):313–320. doi: 10.1111/j.1474-8673.1981.tb00461.x. [DOI] [PubMed] [Google Scholar]
  5. Digges K. G., Summers R. J. Characterization of postsynaptic alpha-adrenoceptors in rat aortic strips and portal veins. Br J Pharmacol. 1983 Jul;79(3):655–665. doi: 10.1111/j.1476-5381.1983.tb10002.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hamilton T. C., Weir S. W., Weston A. H. Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol. 1986 May;88(1):103–111. doi: 10.1111/j.1476-5381.1986.tb09476.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Heinzow B. G., Angus J. A., Korner P. I. Effects of alinidine (ST 567) on baroreceptor-heart rate reflexes and its interactions with clonidine on the baroreflex and on the sympathetic terminals of the isolated atrium. Eur J Pharmacol. 1982 Oct 22;84(3-4):177–187. doi: 10.1016/0014-2999(82)90200-x. [DOI] [PubMed] [Google Scholar]
  8. Hollingsworth M., Amédée T., Edwards D., Mironneau J., Savineau J. P., Small R. C., Weston A. H. The relaxant action of BRL 34915 in rat uterus. Br J Pharmacol. 1987 Aug;91(4):803–813. doi: 10.1111/j.1476-5381.1987.tb11279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Inoue T., Kanmura Y., Fujisawa K., Itoh T., Kuriyama H. Effects of 2-nicotinamidoethyl nitrate (nicorandil; SG-75) and its derivative on smooth muscle cells of the canine mesenteric artery. J Pharmacol Exp Ther. 1984 Jun;229(3):793–802. [PubMed] [Google Scholar]
  10. Malta E., Raper C., Tawa P. E. Pre- and postjunctional effects of clonidine- and oxymetazoline-like compounds in guinea-pig ileal preparations. Br J Pharmacol. 1981 Jun;73(2):355–362. doi: 10.1111/j.1476-5381.1981.tb10429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McPherson G. A., Coupar I. M., Taylor D. A. Competitive antagonism of alpha 1-adrenoceptor mediated pressor responses in the rat mesenteric artery. J Pharm Pharmacol. 1984 May;36(5):338–340. doi: 10.1111/j.2042-7158.1984.tb04389.x. [DOI] [PubMed] [Google Scholar]
  12. Osterrieder W. Modification of K+ conductance of heart cell membrane by BRL 34915. Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):93–97. doi: 10.1007/BF00169483. [DOI] [PubMed] [Google Scholar]
  13. Quast U. Effect of the K+ efflux stimulating vasodilator BRL 34915 on 86Rb+ efflux and spontaneous activity in guinea-pig portal vein. Br J Pharmacol. 1987 Jul;91(3):569–578. doi: 10.1111/j.1476-5381.1987.tb11250.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Scholtysik G. Evidence for inhibition by ICS 205-930 and stimulation by BRL 34915 of K+ conductance in cardiac muscle. Naunyn Schmiedebergs Arch Pharmacol. 1987 Jun;335(6):692–696. doi: 10.1007/BF00166988. [DOI] [PubMed] [Google Scholar]
  15. Taylor S. G., Weston A. H. Endothelium-derived hyperpolarizing factor: a new endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci. 1988 Aug;9(8):272–274. doi: 10.1016/0165-6147(88)90003-x. [DOI] [PubMed] [Google Scholar]
  16. Weir S. W., Weston A. H. Effect of apamin on responses to BRL 34915, nicorandil and other relaxants in the guinea-pig taenia caeci. Br J Pharmacol. 1986 May;88(1):113–120. doi: 10.1111/j.1476-5381.1986.tb09477.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Weir S. W., Weston A. H. The effects of BRL 34915 and nicorandil on electrical and mechanical activity and on 86Rb efflux in rat blood vessels. Br J Pharmacol. 1986 May;88(1):121–128. doi: 10.1111/j.1476-5381.1986.tb09478.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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