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. 1993 Jun;109(2):386–393. doi: 10.1111/j.1476-5381.1993.tb13581.x

Modulation of vasodilatation to levcromakalim by hypoxia and EDRF in the rabbit isolated ear: a comparison with pinacidil, sodium nitroprusside and verapamil.

M D Randall 1, T M Griffith 1
PMCID: PMC2175711  PMID: 8358541

Abstract

1. We have used an isolated buffer-perfused preparation of the rabbit ear to investigate the effects of hypoxia and inhibition of endothelium-derived relaxing factor (EDRF) synthesis on the vasodilator responses to the potassium channel opener, levcromakalim (the active (-)-enantiomer of cromakalim). The results obtained with levcromakalim have been compared with those for pinacidil, sodium nitroprusside and verapamil. 2. Levcromakalim relaxed preconstricted preparations with an EC50 = 343 +/- 41 nM and Rmax = 80.3 +/- 6.4%. Under hypoxic conditions the concentration-response curve was significantly (P < 0.01) shifted to the left with an EC50 = 118 +/- 16 nM and Rmax = 89.9 +/- 2.7%. Hypoxia did not influence relaxation to either pinacidil, sodium nitroprusside or verapamil. 3. Inhibition of EDRF synthesis with 100 microM NG-nitro-L-arginine methyl ester (L-NAME) also significantly (P < 0.001) increased the vasodilator potency of levcromakalim (EC50 = 56 +/- 5 nM), and caused a similar shift in the concentration-response curve to sodium nitroprusside. It did not influence vasodilation to either verapamil or pinacidil. The potentiation of vasodilator responses to levcromakalim by L-NAME was reversed by an excess of L-arginine. 4. Impairment of oxidative phosphorylation with 400 nM carbonyl cyanide m-chlorophenylhydrazone significantly (P < 0.05) increased the potency of levcromakalim (EC50 = 120 +/- 20 nM) but did not influence vasodilation to pinacidil or endothelium-dependent relaxations to acetylcholine. 5. Vasodilatation to levcromakalim was augmented both by hypoxia and by inhibition of EDRF activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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