The possible functional coupling between β₁-adrenoceptor and MaxiK channels which results in smooth muscle relaxation was examined in the guinea-pig esophageal muscularis mucosae. Isoprenaline-elicited relaxation of esophageal smooth muscle was confirmed to be mediated through β₁-adrenoceptors as the response was competitively antagonized by a β₁-selective antagonist atenolol with a pA₂ value of 7.01. Iberiotoxin (IbTx, 10^-7 M), a selective MaxiK channel inhibitor, substantially diminished the relaxant response to isoprenaline. The extent of the MaxiK channel contribution to the relaxant response was 15-40% of the control response when estimated as the E_50%-E_max responses to isoprenaline. The relaxation to isoprenaline was also attenuated by high-KCl (80 mM) to the same degree as the relaxant response generated in the presence of IbTx, and thus the estimated extent of the K⁺ channel contribution was 10-40%. These findings indicate that β₁-adrenoceptors are substantially coupled with MaxiK channels to produce relaxation of esophageal smooth muscle in the guinea-pig. Although MaxiK channels account for the contribution of K⁺ channels to the β₁-adrenoceptor-mediated relaxation in this smooth muscle preparation, their contribution seems to be less when compared to the β₂-adrenoceptor-mediated relaxation of tracheal smooth muscle.

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Our aim was to study a role of nitrergic input in gastric relaxation in conscious dogs. Proximal gastric motor responses to mechanical distension and chemical stimulation (a lipid meal orally) were evaluated by electronic barostat. Effect of N^G-monomethyl-L-arginine acetate (L-NMMA, 5 mg/kg) on these responses was studied. When mechanical stimulation was applied, we observed steep linear increases in intragastric pressure up to about 6 mmHg, then continued to increase gradually, and could be increased still further upon the addition of L-NMMA. Oral application of a lipid led to a prompt fall in intragastric pressure (gastric receptive relaxation; GRR). Lipid treatment also led to a considerable increase in gastric volume (means ± S.D., 150.0 ± 50.2 ml), this was followed by a plateau phase and a gradual return to baseline levels. Neither GRR nor the associated increase in gastric volume (167.6 ± 53.0 ml) was sensitive to treatment with L-NMMA. Our conclusion is that nitrergic input is necessary for mechanically induced gastric relaxation, but not for either GRR or chemically-induced gastric relaxation in conscious dogs.

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The involvement of the superoxide anion in endothelium-dependent relaxation (EDR) was examined in noradrenaline-contracted aortic smooth muscle preparations isolated from normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acetylcholine (ACh, 10^-9-10^-5 M) induced EDR in both WKY and SHRSP preparations in a concentration-dependent manner, but with a significantly smaller amplitude in those from SHRSP than in those from WKY. The ACh-induced EDR was inhibited by N^ω-nitro-L-arginine (L-NOARG), in a concentration-dependent manner, both in WKY and SHRSP. The EDR produced in WKY in the presence of 3 × 10^-6 M L-NOARG was similar in magnitude to that produced in SHRSP in the absence of L-NOARG. Superoxide dismutase (SOD, 300 units/ml) increased the amplitude of EDR in SHRSP but not in WKY, with no alteration of the threshold or of the maximal amplitude. The maximal amplitude of EDR produced in SHRSP in the presence of SOD was still smaller than that in WKY. In WKY, a possible involvement of superoxide in the EDR was examined in aortae whose EDR was partially inhibited by treatment with a subthreshold concentration (3 × 10 ^-6 M) of L-NOARG. In the L-NOARG-conditioned aorta, the reduced EDR was partially but significantly recovered by SOD. These results suggest that the impaired EDR in aortae of SHRSP may be causally related to a higher production of superoxide. The L-NOARG-induced inhibition of EDR in WKY may be produced, in part, by the reduction of effective NO due to its destruction by superoxide.

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