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1 The possibility that stimulation of smooth muscle a 1 -adrenoceptors modulates contraction via the endothelium was examined in rat small mesenteric arteries. 2 N o -nitro-L-arginine methyl ester, (L-NAME, 100 mM to inhibit NO synthase) increased contraction to single concentrations of phenylephrine (1 ± 3 mM) by approximately 2 fold (from a control level of 14.2+3.0 to 34.1+4.2% of the maximum contraction of the artery, n=20). The action of L-NAME was abolished by disrupting the endothelium.3 The subsequent addition of apamin (to inhibit small conductance Ca 2+ -activated K + channels, 50 nM) further augmented phenylephrine contractions, in an endothelium-dependent manner, to more than 3 fold above control (50.4+5.3% of the maximum contraction, n=11). 4 Charybdotoxin (non-selective inhibitor of large conductance Ca 2+ -activated K + channels, BK Ca , 50 nM) plus L-NAME augmented the level of phenylephrine contraction to 4 ± 5-fold above control (64.1+3.1%, n=5), but this e ect was independent of the endothelium. The potentiation of contraction by charybdotoxin could be mimicked with the selective BK Ca inhibitor, iberiotoxin,. 5 Apamin together with L-NAME and charybdotoxin further signi®cantly increased the phenylephrine contraction by 5 ± 6-fold, to 79.9+3.5% of the maximum contraction of the artery (n=13). 6 Phenylephrine failed directly to increase the intracellular Ca 2+ concentration in endothelial cells freshly isolated from the small mesenteric artery. 7 Stimulation of smooth muscle a 1 -adrenoceptors in the mesenteric artery induces contraction that is markedly suppressed by the endothelium. The attenuation of contraction appears to re¯ect both the release of NO from the endothelium and the e ux of K + from both endothelial and smooth muscle cells. This suggests that the release of NO and endothelium-derived hyperpolarizing factor can be evoked indirectly by agents which act only on the smooth muscle cells.

It is widely established that in rat mesenteric arteries, endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation evoked by acetylcholine is abolished by a combination of charybdotoxin plus apamin. 4-Aminopyridine, an inhibitor of voltage-gated (Kv) K + -channels, in combination with apamin had moderate effects on the EDHF-mediated relaxation. Maurotoxin (MTX), an inhibitor of Kv and intermediate-conductance Ca 2+ -activated K + -channels (IK), had no effect on EDHF-mediated relaxation. However, MTX in combination with apamin completely abolished EDHF-mediated relaxation and endothelial cell hyperpolarization. The selective IK inhibitor 2-(2-chlorophenyl)-2,2-diphenyl acetonitrile (TRAM-39) had no significant effect on EDHF-mediated relaxation. EDHF-mediated vasorelaxation and hyperpolarization was abolished by a combination of TRAM-39 and apamin. These data demonstrate two new combinations of K + -channel inhibitors for the investigation of EDHF. Furthermore, by using TRAM-39, a potent selective inhibitor of IK channels, we provide the first direct evidence that abolition of EDHF requires the simultaneous presence of intermediate-and small-conductance Ca 2+ -activated K + -channel inhibitors.

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(1994) found longer lexical-decision latencies to 4-letter words when an ambiguous letter (one from which neighbors could be formed) was delayed than when an unambiguous letter (one from which no neighbors could be formed) was delayed. They suggested that this was due to competition between partially activated words. However, K. I. Forster and D. Shen (1996) suggested that this effect may be due to participants' generating hypotheses on the basis of the previewed trigram. The authors conducted 2 experiments that used a partial priming methodology and found that lexicaldecision latencies were longer to words preceded by ambiguous trigrams than unambiguous trigrams when (a) the target was the highest frequency member in its neighborhood and (b) the prime was masked and presented for 60 ms. These results are inconsistent with Forster and Shen's prediction of no effect of prime ambiguity under these conditions, and they indicate that the ambiguity effect was not due to hypothesis generation on the basis of the partial primes.