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Abstract

Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine, acetylcholine and nitric oxide.

S A Khan, W R Mathews and K D Meisheri
Journal of Pharmacology and Experimental Therapeutics December 1993, 267 (3) 1327-1335;
S A Khan
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W R Mathews
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K D Meisheri
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Abstract

A comparative analysis was carried out of the sensitivities of in vitro vasorelaxations by nitroglycerine (NTG), acetylcholine (ACh) and nitric oxide (NO) to blockade by glyburide, a blocker of ATP-sensitive K+ channels (KATP), as well as to blockade by charybdotoxin (ChTX) and iberiotoxin (lbTX), potent blockers of calcium-activated K+ channels (KCa). In the isolated rabbit mesenteric artery (RMA) precontracted with 5 microM norepinephrine (NE), ACh (0.01-1 microM), NTG (0.01-5 microM) and NO (0.075-2.7 microM) produced a dose-dependent vasodilation. Glyburide (0.5 microM) had no significant effect on relaxation dose-response curves (DRCs) to ACh, NTG or NO. In contrast, glyburide completely abolished the relaxation DRC by pinacidil, a known KATP opener. ChTX (10 or 100 nM) caused an inhibition of relaxation DRCs to ACh, NTG and NO. In all cases, ChTX shifted the relaxation DRC to the right and depressed the maximal response. Another potent KCa blocker, lbTX (20 nM) also significantly inhibited relaxation DRCs to NTG, ACh and NO and inhibited maximal relaxation response to SNP. The effects of ChTX and lbTX were selective; they did not inhibit relaxations by pinacidil and forskolin. Finally, it was observed that the use of 80 mM K+ as a contractile stimulus inhibited NTG relaxations in a manner similar to the KCa blockers. Collectively, these data provide strong support for the hypothesis that the activation of KCa plays an important role in mediating the vasorelaxation caused by NTG, SNP, ACh and NO.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 267, Issue 3
1 Dec 1993
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Abstract

Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine, acetylcholine and nitric oxide.

S A Khan, W R Mathews and K D Meisheri
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1327-1335;

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Abstract

Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine, acetylcholine and nitric oxide.

S A Khan, W R Mathews and K D Meisheri
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1327-1335;
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