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. 1988 Sep;95(1):103–108. doi: 10.1111/j.1476-5381.1988.tb16553.x

Pinacidil opens K+-selective channels causing hyperpolarization and relaxation of noradrenaline contractions in rat mesenteric resistance vessels.

L M Videbaek 1, C Aalkjaer 1, M J Mulvany 1
PMCID: PMC1854119  PMID: 3219470

Abstract

1. The effects of pinacidil on noradrenaline-induced tone, smooth muscle membrane potential and 42K- and 86Rb-efflux from isolated mesenteric resistance vessels (internal diameter 200 microns) of the rat have been studied. 2. Pinacidil (0.3-10 microM) produced concentration-dependent suppression of noradrenaline-induced tone. 3. Pinacidil (0.3-10 microM) caused concentration-dependent hyperpolarization of the smooth muscle. 4. In rat resistance vessels loaded with 42K, pinacidil (1-10 microM) significantly increased the 42K-efflux rate constant. 5. With the use of 86Rb as a marker for K+, 1 microM pinacidil did not affect the 86Rb-efflux rate constant, while 10 microM pinacidil transiently increased the 86Rb rate constant. 6. The results indicate that the relaxant action of pinacidil in these vessels is due to the opening of K+-channels and consequent hyperpolarization. The K+-channels opened are selective for 42K over 86Rb.

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Selected References

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  1. Aalkjaer C., Mulvany M. J. Sodium metabolism in rat resistance vessels. J Physiol. 1983 Oct;343:105–116. doi: 10.1113/jphysiol.1983.sp014883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arrigoni-Martelli E., Nielsen C. K., Olsen U. B., Petersen H. J. N''-cyano-N-4-pyridyl-N'-1,2,2-trimethylpropylguanidine, monohydrate (P 1134): a new, potent vasodilator. Experientia. 1980 Apr 15;36(4):445–447. doi: 10.1007/BF01975139. [DOI] [PubMed] [Google Scholar]
  3. Bohlen H. G. Localization of vascular resistance changes during hypertension. Hypertension. 1986 Mar;8(3):181–183. doi: 10.1161/01.hyp.8.3.181. [DOI] [PubMed] [Google Scholar]
  4. Bray K. M., Newgreen D. T., Small R. C., Southerton J. S., Taylor S. G., Weir S. W., Weston A. H. Evidence that the mechanism of the inhibitory action of pinacidil in rat and guinea-pig smooth muscle differs from that of glyceryl trinitrate. Br J Pharmacol. 1987 Jun;91(2):421–429. doi: 10.1111/j.1476-5381.1987.tb10297.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carlsen J. E., Kardel T., Hilden T., Tangø M., Trap-Jensen J. Immediate central and peripheral haemodynamic effects of a new vasodilating agent Pinacidil (P1134) in hypertensive man. Clin Physiol. 1981 Aug;1(4):375–384. doi: 10.1111/j.1475-097x.1981.tb00905.x. [DOI] [PubMed] [Google Scholar]
  6. Cook N. S., Quast U., Hof R. P., Baumlin Y., Pally C. Similarities in the mechanism of action of two new vasodilator drugs: pinacidil and BRL 34915. J Cardiovasc Pharmacol. 1988 Jan;11(1):90–99. doi: 10.1097/00005344-198801000-00014. [DOI] [PubMed] [Google Scholar]
  7. Eilertsen E., Hart J. W., Magnussen M. P., Sørensen H., Arrigoni-Martelli E. Pharmacokinetics and distribution of the new antihypertensive agent pinacidil in rat, dog and man. Xenobiotica. 1982 Mar;12(3):177–185. doi: 10.3109/00498258209046792. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Kauffman R. F., Schenck K. W., Conery B. G., Cohen M. L. Effects of pinacidil on serotonin-induced contractions and cyclic nucleotide levels in isolated rat aortae: comparison with nitroglycerin, minoxidil, and hydralazine. J Cardiovasc Pharmacol. 1986 Nov-Dec;8(6):1195–1200. doi: 10.1097/00005344-198611000-00015. [DOI] [PubMed] [Google Scholar]
  10. Latorre R., Miller C. Conduction and selectivity in potassium channels. J Membr Biol. 1983;71(1-2):11–30. doi: 10.1007/BF01870671. [DOI] [PubMed] [Google Scholar]
  11. Mulvany M. J., Halpern W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res. 1977 Jul;41(1):19–26. doi: 10.1161/01.res.41.1.19. [DOI] [PubMed] [Google Scholar]
  12. Mulvany M. J., Nilsson H., Flatman J. A. Role of membrane potential in the response of rat small mesenteric arteries to exogenous noradrenaline stimulation. J Physiol. 1982 Nov;332:363–373. doi: 10.1113/jphysiol.1982.sp014418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Smith J. M., Sanchez A. A., Jones A. W. Comparison of rubidium-86 and potassium-42 fluxes in rat aorta. Blood Vessels. 1986;23(6):297–309. doi: 10.1159/000158657. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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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