In vitro investigation of the bladder-vascular selectivity of levcromakalim and YM934 in human tissues

R. Chess-Williams, S. W. Martin, C. Korstanje, C. R. Chapple

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Abstract

Objective. To examine the potencies of the potassium-channel openers (KCOs) levcromakalim and YM934 as relaxing agents on human detrusor and human mesenteric artery smooth muscle, and to determine their bladder-vascular selectivity in vitro. Materials and methods. Strips of human detrusor muscle and mesenteric artery (with the endothelium removed) were set up in physiological salt solution and the tension developed by the tissues recorded. Tissues were precontracted with a concentration of carbachol (detrusor) or phenylephrine (artery) which caused 80% of maximal contraction, and relaxation responses to levcromakalim and YM934 were then obtained. Results. Both KCOs caused relaxation of the bladder detrusor muscle and the mesenteric artery. Maximal responses, when plotted as a percentage of the precontraction, were greater for both KCOs in the bladder muscle than the artery, but the differences were small and not statistically significant. The sensitivity (drug potency) of the detrusor muscle to the KCOs was more than twice that of the artery but this selectivity was only statistically significant for YM934. Conclusions. Only minor bladder-vascular selectivity for levcromakalim and YM934 could be detected in vitro. This suggests that neither drug would be tolerated clinically, although the results suggest that further development of bladder-selective KCO agents appears feasible.

Original languageEnglish
Pages (from-to)1050-1054
Number of pages5
JournalBJU International
Volume83
Issue number9
DOIs
Publication statusPublished - 1999
Externally publishedYes

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Cromakalim
Blood Vessels
Urinary Bladder
Mesenteric Arteries
Muscles
Arteries
Potassium Channels
Carbachol
Phenylephrine
Pharmaceutical Preparations
Endothelium
Smooth Muscle
Salts
2H-1,4-benzoxazine, 3,4-dihydro-2,2-dimethyl-6-nitro-4-(2-pyridinyl)-, N-oxide
In Vitro Techniques

Cite this

Chess-Williams, R. ; Martin, S. W. ; Korstanje, C. ; Chapple, C. R. / In vitro investigation of the bladder-vascular selectivity of levcromakalim and YM934 in human tissues. In: BJU International. 1999 ; Vol. 83, No. 9. pp. 1050-1054.
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abstract = "Objective. To examine the potencies of the potassium-channel openers (KCOs) levcromakalim and YM934 as relaxing agents on human detrusor and human mesenteric artery smooth muscle, and to determine their bladder-vascular selectivity in vitro. Materials and methods. Strips of human detrusor muscle and mesenteric artery (with the endothelium removed) were set up in physiological salt solution and the tension developed by the tissues recorded. Tissues were precontracted with a concentration of carbachol (detrusor) or phenylephrine (artery) which caused 80{\%} of maximal contraction, and relaxation responses to levcromakalim and YM934 were then obtained. Results. Both KCOs caused relaxation of the bladder detrusor muscle and the mesenteric artery. Maximal responses, when plotted as a percentage of the precontraction, were greater for both KCOs in the bladder muscle than the artery, but the differences were small and not statistically significant. The sensitivity (drug potency) of the detrusor muscle to the KCOs was more than twice that of the artery but this selectivity was only statistically significant for YM934. Conclusions. Only minor bladder-vascular selectivity for levcromakalim and YM934 could be detected in vitro. This suggests that neither drug would be tolerated clinically, although the results suggest that further development of bladder-selective KCO agents appears feasible.",
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In vitro investigation of the bladder-vascular selectivity of levcromakalim and YM934 in human tissues. / Chess-Williams, R.; Martin, S. W.; Korstanje, C.; Chapple, C. R.

In: BJU International, Vol. 83, No. 9, 1999, p. 1050-1054.

Research output: Contribution to journalArticleResearchpeer-review

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N2 - Objective. To examine the potencies of the potassium-channel openers (KCOs) levcromakalim and YM934 as relaxing agents on human detrusor and human mesenteric artery smooth muscle, and to determine their bladder-vascular selectivity in vitro. Materials and methods. Strips of human detrusor muscle and mesenteric artery (with the endothelium removed) were set up in physiological salt solution and the tension developed by the tissues recorded. Tissues were precontracted with a concentration of carbachol (detrusor) or phenylephrine (artery) which caused 80% of maximal contraction, and relaxation responses to levcromakalim and YM934 were then obtained. Results. Both KCOs caused relaxation of the bladder detrusor muscle and the mesenteric artery. Maximal responses, when plotted as a percentage of the precontraction, were greater for both KCOs in the bladder muscle than the artery, but the differences were small and not statistically significant. The sensitivity (drug potency) of the detrusor muscle to the KCOs was more than twice that of the artery but this selectivity was only statistically significant for YM934. Conclusions. Only minor bladder-vascular selectivity for levcromakalim and YM934 could be detected in vitro. This suggests that neither drug would be tolerated clinically, although the results suggest that further development of bladder-selective KCO agents appears feasible.

AB - Objective. To examine the potencies of the potassium-channel openers (KCOs) levcromakalim and YM934 as relaxing agents on human detrusor and human mesenteric artery smooth muscle, and to determine their bladder-vascular selectivity in vitro. Materials and methods. Strips of human detrusor muscle and mesenteric artery (with the endothelium removed) were set up in physiological salt solution and the tension developed by the tissues recorded. Tissues were precontracted with a concentration of carbachol (detrusor) or phenylephrine (artery) which caused 80% of maximal contraction, and relaxation responses to levcromakalim and YM934 were then obtained. Results. Both KCOs caused relaxation of the bladder detrusor muscle and the mesenteric artery. Maximal responses, when plotted as a percentage of the precontraction, were greater for both KCOs in the bladder muscle than the artery, but the differences were small and not statistically significant. The sensitivity (drug potency) of the detrusor muscle to the KCOs was more than twice that of the artery but this selectivity was only statistically significant for YM934. Conclusions. Only minor bladder-vascular selectivity for levcromakalim and YM934 could be detected in vitro. This suggests that neither drug would be tolerated clinically, although the results suggest that further development of bladder-selective KCO agents appears feasible.

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