A study was made on the relatively immediate relaxant effect of cholera toxin (CTX) on the isolated ear artery, thoracic aorta and saphenous vein of the rabbit. Both preparations of CTX, containing sodium azide (NaN₃) and azide-free, showed no effect on the non-precontracted artery, but CTX containing NaN₃ relaxed the moderately precontracted blood vessels with methoxamine promptly, i. e., with a time course of min order. However, the immediate relaxation produced by CTX containing NaN₃ was attributed mainly to NaN₃. Azide-free CTX, on the other hand, at 1-10 μg/ml gradually produced concentra- tion-dependent relaxation of the precontracted vessels. The relaxant effects of CTX on the vessels were slow and long-lasting, i. e., with a time course of 10 min order. The relaxation induced by CTX was not influenced by the removal of endothelium nor by pretreatment with 10μM indomethacin, 3 μM atropine or 3 μM propranolol. Activation of protein kinase C by a phorbol ester inhibited the relaxant effect of CTX. These results indicate that CTX relaxes the blood vessels by directly acting on the smooth muscles, without mediation by known endogenous relaxing factor, such as endothelium-derived relaxing factor (EDRF=NO) or prostaglandin I₂ (prostacyclin) and by muscarinic receptor or β-adrenoceptor.

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Mechanisms of elevation of active tone in arterial smooth muscle of spontaneously hypertensive rats and effects of antihypertensive treatments are reviewed. Spontaneously hypertensive rats are created by Okamoto et al. and classified mainly into three strains, SHR, SHRSP and M-SHRSP. Blood pressure of the rats is higher in this order. The aortic smooth muscle of these rats exhibits elevation of the active tension (tone) under non-stimulated condition. The active tone is greater as the blood pressure of the rats elevated and good correlation between blood pressure and active tone can be obtained. The active tone is sensitive to extracellular Ca and abolished by the removal of extracellular Ca or by the application of Ca-antagonists. It is also associated with increased intracellular Ca level. These results indicate that the active tone is brought about by increase in voltage-dependent Ca channel opening of the cell membrane. Increased voltage-dependent Ca channel opening, i. e. membrane depolarization and increased inward Ca current can be a cause of the elevated tone. Abnormalities in the cellular mechanisms for relaxation of the smooth muscle can also contribute to the elevation of the active tone. Endothelium suppres-ses the active tone, probably releasing endothelium-derived relaxing factor or hyperpolariz-ing factor. The suppression of contraction by endothelium is impaired in the blood vessels of spontaneously hypertensive rats, depending on the degree of hypertension. Antihyperten- sive treatments prevent the development or elevation of the active tone. It also prevents the impairment of function of endothelium. Thus, the maintained hypertension alteres functions of smooth muscle membrane and endothelium. The degree and duration of hypertension are thought to be determinant factors of these abnormalities.

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Effects of various histamine H₂-receptor antagonists (H₂-RA) on gastrointestinal motility and gastric emptying were investigated.
Ranitidine, nizatidine and cimetidine dose dependently induced contractions over the entire gastrointestinal tract, and the order of their effects was ranitidine>nizatidine>cimetidine.
Roxatidine or famotidine had no effects on motility of the gastrointestinal tract.
Ranitidine and nizatidine also induced contractions during the postprandial period and facilitated gastric emptying, while cimetidine, roxatidine or famotidine did not influence gastric emptying.
Since acid reduction is thought to be the most important element of the treatment of peptic ulcer and reflux esophagitis, it was inferred that administration of a H₂-RA selected with consideration of its property of facilitating gastrointestinal motility is effective in the treatment of patients with abnormal gastrointestinal motility.

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