Although serotonin (5-hydroxytryptamine, 5-HT) has been found to be a potent vasoconstrictor, a pivotal role of 5-HT in the control of appetite and mood control by the modulation of neuronal synapse has also been proposed. Selective 5-HT reuptake inhibitors (SSRIs) are frequently used to suppress appetite and treat depressive disorder, and the target protein of SSRIs is the 5-HT transporter (5-HTT) in the neuronal synapse. However, SSRIs may increase the free 5-HT concentration in circulating blood because platelets and vascular smooth muscles express functional 5-HTT. In addition, enhanced vasoactive action of 5-HT and alterations in 5-HT receptor subtypes have been reported in some types of hypertension. Therefore, we can infer that the use of drugs such as SSRIs in some hypertensive patients is potentially risky. Altered functional expression of ion channels in vascular smooth muscle is suggested to be a mechanism for the enhanced vasoconstriction by vasoactive agonists, including 5-HT. In this brief review, we compared the electrophysiological properties of mesenteric artery myocytes and their modulation by 5-HT between sham-operated control and deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
The 13C-octanoic acid breath test is widely used for evaluating gastric emptying of solids. Since the results of this test are influenced by multiple factors such as the time required to grind the solid meal into smaller particles, the gastroduodenal transport time of the ground meal, and the time required for bowel drug absorption and drug dispersion, the administration of a test meal by the oral route alone cannot result in an accurate measurement of the complicated process of emptying the stomach of solids. The aim of the present study was to evaluate each phase of gastric emptying of solids by varying the administration route of the test meal. Six healthy male volunteers (mean age: 33.2 yr) participated in the study. The test meal consisted of a bowl of rice topped with a mixture of boiled chicken and eggs admixed with 100 mg of 13C-octanoic acid (total: 273 kcal). All subjects were given the test meal by each of the following three methods: 1. Normal oral intake of the test meal, 2. Feeding of the ground test meal through a nasogastric tube, 3. Feeding of the ground test meal through a duodenal tube. For each set of examinations, the mean residence time (MRT), half-emptying time (T1/2), gastric emptying coefficient (GEC), lag phase (L-breath), and measured maximum 13C excretion time (Tmax-measured) were calculated. The data was analyzed to determine the time for each phase of gastric emptying as follows: mean grinding time (MGT) = MRToral - MRTnasogastric, mean gastroduodenal transport time (MGDTT) = MRTnasogastric - MRT nasoduodenal. Data was expressed as the mean ± SE. The values of the parameters of MGT were 0.82 ± 0.50 hr (MRT), 0.64 ± 0.18 hr (T1/2), 0.51 ± 0.24 hr (L-breath), -0.45 ± 0.30 hr (GEC), and 49.2 ± 8.0 min (Tmax-measured). The values of the parameters of MGDTT were 0.87 ± 0.38 hr (MRT), 0.26 ± 0.29 hr (T1/2), 0.92 ± 0.36 hr (L-breath), 0.55 ± 0.23 hr (GEC), and 63.33 ± 8.16 min (Tmax-measured). The times required for the drug absorption and disposition were 1.60 0.20 hr (MRT), 1.03 ± 0.24 hr (T1/2), 0.10 ± 0.08 hr (L-breath), 3.72 ± 0.46 hr (GEC), and 19.67 ± 2.11 min (Tmax-measured). By varying the administration route of a test meal containing 13C-octanoic acid, we may be able to assess each phase of the emptying of gastric solids in detail, thus leading to a better understanding of gastroduodenal motility.
In our previous report, we showed that L-arginine induced depolarization of smooth muscle cells of the rat portal vein with an increased contraction. To clarify the ionic mechanism of the membrane depolarization, the effect of L-arginine on the holding current was studied in freshly isolated smooth muscle cells of the rat portal vein. The whole-cell patch-clamp technique was used, with the membrane potential held at -60 mV. In the presence of Na+ in the perfusate, L-arginine 10 mM induced an inward current in about 50% of the cells. In Na+-deficient perfusate, L-arginine 10 mM increased the amplitude of the inward current in a Na+ concentration-dependent manner. BCH, an inhibitor of the Na+-dependent amino acid transporter, ceased the L-arginine-induced current. These results indicate that L-arginine induces an inward current via Na +-dependent mechanisms in rat portal venous smooth muscle cells.