We studied rat mesenteric arterial beds to determine the relationship between the effects of flow-induced shear stress and agonists on mesenteric vasoreactivity. When beds were perfused at gradually increasing flow rates, perfusion pressure was flow rate-dependently increased. The flow rate-mediated increase in perfusion pressure was significantly enhanced by N^G-nitro-L-arginine (L-NOARG) plus methylene blue (MB) and slightly enhanced by treatment with tetraethylammonium (TEA). In the presence of L-NOARG, MB, TEA, and indomethacin, the flow rate-induced increase in perfusion pressure was significantly enhanced, but this enhancement was significantly inhibited by combined treatment with BQ-123 plus BQ-788 (ET_A- and ET_B- receptor antagonists, respectively). The ET-1 content of the perfusate was significantly increased following combined pretreatment with L-NOARG, MB, TEA, and indomethacin at a high flow rate. The methoxamine-induced contraction was significantly enhanced by NOS inhibition in both high- and low- flow-treated groups. The released nitrite level was significantly greater in high-flow-loaded than in the low-flow-loaded beds. We conclude that in this model, the response of vascular tone to flow stimulation is subtly regulated by endothelium-derived factors (especially, NO, endothelium-derived hyperpolarizing factor, and ET-1), and that these factors interact with each other.

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The aim of this study was to evaluate the motor activity of the interposed colonic segment in patients who had received a colonic replacement following radical esophagectomy using spectral analysis and a 24 hr activity graph. The 24-hr ambulatory pressure waves were recorded in the replaced colon after esophagectomy (n=8) using a solid-state manometric catheter (MicroDigitrapper, Synetics). Motility and spectral analyses of the intraluminal pressure waves were performed by Multigram and Gastrosoft (Synetics). It was revealed that after a meal the 3 cpm (cycles per minute) component of the motility index increased but the 12-15 cpm component decreased. The diurnal rhythm showed that colonic motility was high in the daytime and low during sleep. In contrast, duodenal motility was relatively high even during sleep. The motility index increased as the postoperative period increased. The motility of the replaced colon was higher during the daytime and after meals. The higher motility after meals was characterized by an increase in the 3 cpm component. These motor characteristics may help the function of the replaced colon as a substitute for the esophagus.

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While nonspecific airway hyperresponsiveness (AHR) is a central feature of allergic bronchial asthma, the mechanism underlying the developmont of AHR is not clearly understood. We have previously demonstrated in vitro hyperresponsiveness of bronchial smooth muscle to acetylcholine (ACh) in rats that were actively sensitized and repeatedly challenged with aerosolized antigen. It has also been demonstrated that the ACh-induced, RhoA-mediated Ca²⁺ sensitization is markedly augmented concomitantly with an increased expression and activation of RhoA protein in the bronchial smooth muscle of the antigen-treated rats. In the present study, we have investigated whether TNF-α, a proinflammatory cytokine which is involved in bronchial asthma, causes upregulation of RhoA mRNA and protein in the rat bronchus. Treatment of rat bronchial smooth muscle preparations with TNF-α (300 ng/ml for 24 hr) significantly shifted the concentration-response curve to ACh upwards, but did not alter the response to high K⁺, when compared to that of control tissues. Levels of RhoA mRNA and protein in the TNF-α-treated bronchus were significantly greater than those in the control group. In conclusion, it is suggested that the augmentation of the ACh-induced contractile response evoked by TNF-α might be mediated by an upregulation of RhoA in rat bronchial smooth muscle.

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A Na⁺/Ca²⁺ exchanger (NCX) is one of the major regulators of intracellular Ca²⁺ concentration ([Ca²⁺]_i) in cardiac muscle cells. Although vascular smooth muscle myocytes also express NCX proteins, their functional role has not been clear, mainly due to the lack of specific inhibitors of NCX and relatively low levels of expression of NCX. In the present study, we have examined the involvement of NCX in the Na⁺ deficient (0 Na⁺) elevation of [Ca²⁺]_i in rat carotid arterial myocytes using KB-R7943, an inhibitor of NCX. Perfusion with a Na⁺-free bathing solution, prepared by replacement of Na⁺ with N-methyl-D-glucamine, induced an elevation of [Ca²⁺]_i, which was effectively inhibited by KB-R7943 (IC₅₀=3.5 μM). This inhibition was reversed by washout of KB-R7943. In contrast, D600, a blocker of voltage dependent L-type Ca²⁺ channels (VDCC), did not affect the 0 Na⁺-induced elevation of [Ca²⁺]_i. Treatment of myocytes with ryanodine abolished the elevation of [Ca²⁺]_i caused by caffeine but not that caused by 0 Na⁺. Application of Cd²⁺, which is known to block NCX as well as VDCC, also significantly inhibited the 0 Na⁺ induced elevation. These results suggest that KB-R7943 inhibits the extracellular Na⁺ dependent ([Na⁺]_o) change in [Ca²⁺]_i in rat carotid arterial myocytes, which is presumably activated by the reverse mode of NCX.

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