Biomedical subjects

Akikazu Takada

Publications and source records attributed to Akikazu Takada.

5 recordsLinked to original sources

PubMed2002

L-158,809 and (D-Ala(7))-angiotensin I/II (1-7) decrease PAI-1 release from human umbilical vein endothelial cells.

The endothelium is a major source of plasminogen activator inhibitor-1 (PAI-1), which plays a critical role in the regulation of fibrinolysis. There are many reports on the increase in the expression of PAI-1 by angiotensin II (Ang II). In the present study, we investigated the effects of angiotensin-related substances on the release of PAI-1 from human umbilical vein endothelial cells (HUVECs). Ang II increased PAI-1 and tissue plasminogen activator (t-PA) release, while its metabolite angiotensin-(1-7) (Ang-(1-7)) amino acid fragment decreased them. Angiotensin Type 1 (AT1) receptor antagonist, L-158,809 (L-1), and Ang-(1-7) receptor antagonist, (D-Ala(7))-angiotensin I/II (1-7) (D-Ala), decreased PAI-1 and t-PA release; angiotensin Type 2 (AT2) antagonist, PD123,319 (PD), however, did not have any effects on the release of PAI-1 and t-PA. The addition of the equal concentration or 10-times-higher concentration of L-1 to Ang II did not change PAI-1 release compared to that by Ang II. Although Ang-(1-7) and L-1 decreased PAI-1 release, there were no additional effects on the decrease of the amounts of PAI-1 by the mixture of Ang-(1-7) and the equal concentration or 10-times-higher concentration of L-1 compared to those by Ang-(1-7). The equal concentration of D-Ala to Ang II did not change the amounts of PAI-1, but the addition of the 10-times-higher concentration of D-Ala to Ang II resulted in significant decrease of the amounts of PAI-1 compared to those by Ang II. The addition of equal concentration or 10-times-higher concentration of D-Ala to Ang-(1-7) showed the significant decrease of the amounts of PAI-1 compared to those by Ang-(1-7). In conclusion, L-158,809 and (D-Ala(7))-angiotensin I/III (1-7) may be used as profibrinolytic drugs.

Angiotensin I↗

PubMed2002

Enhanced secretion of tissue plasminogen activator by simultaneous use of retinoic acid and ascorbic acid from tissue cultured gastroepiploic artery.

Tissue-type plasminogen activator (tPA) is a key enzyme in the fibrinolysis system and the regulation of its expression has been extensively studied in cultured vascular endothelial cells. Many kinds of supplements including growth factors are needed, however, to keep endothelial cells viable, which leads the culture condition far from the physiological milieu. Using a new device of amorphous calcium phosphate coated culture plate, we succeeded in culturing ring-cut gastroepiploic artery in a basic medium of RPMI 1640 containing 10% fetal calf serum. The overall normal vessel architecture and the antigenicity of von Willebrand factor, tPA and plasminogen activator inhibitor type 1 (PAI-1) were retained for at least 9 days. tPA was constantly secreted into the conditioned medium at least up to day 12. Employing this organ culture technique, we analyzed the effects of two well-known profibrinolytic vitamins of retinoic acid (Vit. A) and ascorbic acid (Vit. C) on the release of tPA and PAI-1. The cultured artery responded well and the tPA secretion was enhanced by factors of 1.5 fold by Vit. A, 1.7 fold by Vit C and 3.2 fold by their combination, whereas none of these stimuli increased PAI-1 secretion. These results suggested that the cultured ring-cut artery retained functional endothelial cells for at least 9 days and was suitable in analyzing the regulatory mechanism of protein synthesis and secretion from the vascular wall. Using this method, vitamins A and C were shown to lead the intravascular condition to a profibrinolytic state.

Ascorbic Acid↗

PubMed2002

5-HT4 receptors in the hippocampus modulate rat locomotor activity.

In the present study, the ability of 5-hydroxytryptamine-4 (5-HT4) receptors in the hippocampus to enhance locomotor activity in rats was investigated by local infusion via microdialysis probes. The local infusion of 5-HT bilaterally into the striatum did not alter rat motor activity. The local infusion of 1.0 mM 5-HT into the bilateral hippocampus, but not lower doses, significantly increased motor activity as compared with the baseline values or the control rats. During the day hours (0700-1900, light on), the local infusion of either 5-HT4 agonist, 5-MeOT (100 microM) or mosapride (10 microM), but not in their lower concentrations, into the bilateral hippocampus significantly increased motor activity as compared with the baseline values or the control rats. Almost all increased motor activity was normal forward locomotion. This 5-MeOT-induced hyperlocomotion was completely reversed by the combined infusion of a 5-HT4 antagonist, either GR125487D (100 microM), SB204070 (100 microM) or RS23597-190 (100 microM). During the night hours (1900-0700, light off), the local infusion of either SB204070 (100 microM) or RS23597-190 (100 microM), but not in their lower concentrations, into the bilateral hippocampus significantly decreased rat motor activity and inhibited rat nocturnal hyperactivity. These hypoactivities during the night hours induced by 5-HT4 antagonist were reversed by the combined infusion of a 5-HT4 agonist, 5-MeOT (100 microM). The present study demonstrates that the serotonergic neurons projecting to the hippocampus, but not to the striatum, modulate rat locomotor activity by stimulating 5-HT4 receptors in the hippocampus.

Animals↗

PubMed2002

Effects of immunosuppressive drugs on platelet aggregation in vitro.

Disturbances in platelet functions are found in kidney diseases and may contribute to the progression of atherosclerosis with its thrombotic complications. Kidney allograft recipients are particularly prone to dyslipidemia and have a high risk of cardiovascular death. The purpose of this work was to assess effects of various immunosuppressive drugs on aggregation of platelets obtained from healthy volunteers and chronically hemodialyzed patients. Platelet aggregation in the whole blood and in PRP was induced by collagen (2-microgram/ml whole blood and PRP) arachidonic acid (0.75 mM whole blood and PRP), ADP (10 microM--whole blood and 5 microM--PRP), ristocetin (0.75 mg/ml--whole blood and 1.5 mg/ml--PRP) and was studied after preincubation with clinically relevant concentrations of cyclosporine A, FK 506, 15-deoxyspergualin, azathioprine, mizoribine, mycophenolic acid and mycophenolate mofetil. Preincubation with cyclosporine A resulted in a significant increase in platelet aggregation, whereas preincubation with FK 506, azathioprine, mizoribine, mycophenolic acid and mycophenolate mofetil caused a decrease in platelet aggregation. 15-deoxyspergualin did not affect platelet aggregation. Enhanced platelet aggregation in CSA-treated kidney allograft recipients may have clinical implications in regard to the reported tendency to thrombosis in those patients, and to CSA-induced nephrotoxicity. Thus, inhibition of platelet activity in these patients might be of clinical benefit.

Humans↗

PubMedDate not supplied

Effects of a long-term pharmacological interruption of the renin-angiotensin system on the fibrinolytic system in essential hypertension.

To assess the effects of pharmacological interruption of the renin-angiotensin system on the fibrinolysis, tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor-1 antigens (PAI-1) and neurohormones, such as plasma renin activity, norepinephrine, angiotensin II (AII) and IV (AIV) concentrations, were measured in 60 hypertensives. Among them, 48 patients were divided into two groups (25 with 10-20 mg quinapril and 23 with 50-100 mg losartan) who received the drug for 6 months. AII had a weak positive correlation with free PAI-I (n = 60, r = 0.26, p < 0.05) whereas AIV had a strong positive correlation with free PAI-I (n = 60, r = 0.57, p < 0.0001). In both treatment groups, blood pressures were significantly reduced to similar levels after drug treatment. While plasma renin activity increased significantly in both groups after drug treatment, only the losartan group showed significant increases in AII and AIV concentrations. In the quinapril group, there was a significant change in t-PA (p < 0.001) without changes in PAI-1. In the losartan group, free PAI-I and total PAI-I (p < 0.05 for free PAI-I and p < 0.04 for total PAI-I) were significantly increased without a change in t-PA. Thus, quinapril enhanced fibrinolysis but losartan attenuated it. These unique effects of each drug on the fibrinolytic system appear to be associated with changes in AII and AIV concentrations.

Adult↗