[show abstract][hide abstract] ABSTRACT: Background and Purpose
Clinical studies indicate that statins have a BP-lowering effect in hypercholesterolemic individuals with hypertension. Specifically, statins modulate BP through the up-regulation of endothelial NOS (eNOS) activation in the brain. However, the signalling mechanisms through which statins enhance eNOS activation remain unclear. Therefore, we examined the possible signalling pathways involved in statin-mediated BP regulation in the nucleus tractus solitarii (NTS).
To investigate the involvement of Ras and other signalling pathways in simvastatin-induced effects on BP, BP and renal sympathetic nerve activity (RSNA) were determined in spontaneously hypertensive rats (SHRs) before and after i.c.v. administration of simvastatin in the absence and presence of a Ras-specific inhibitor (farnesyl thiosalicylic acid, FTS), a geranylgeranyltransferase inhibitor (GGTI-2133), a PI3K inhibitor (LY294002) or a MAPK-ERK kinase (MEK) inhibitor (PD98059).
FTS significantly attenuated the decrease in BP and increased NO evoked by simvastatin and reversed the decrease in basal RSNA induced by simvastatin. Immunoblotting and pharmacological studies showed that inhibition of Ras activity by FTS significantly abolished simvastatin-induced phosphorylation of ERK1/2, ribosomal protein S6 kinase (RSK), Akt and decreased eNOS phosphorylation. Likewise, administration of Akt and ERK1/2 signalling inhibitors, LY294002 and PD98059, attenuated the reduction in BP evoked by simvastatin. Furthermore, i.c.v. simvastatin decreased Rac1 activation and the number of ROS-positive cells in the NTS.
Conclusions and Implications
Simvastatin modulates central BP control in the NTS of SHRs by increasing Ras-mediated activation of the PI3K-Akt and ERK1/2-RSK signalling pathways, which then up-regulates eNOS activation.
British Journal of Pharmacology 10/2013; 170(4):847-858. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent evidence has suggested that nicotine decreases blood pressure (BP) and heart rate (HR) in the nucleus tractus solitarii (NTS), indicating that nicotinic acetylcholine receptors (nAChRs) play an important role in BP control in the NTS. However, the signalling mechanisms involved in nAChR-mediated depressor effects in the NTS are unclear. Hence, the aim of this study was to investigate these signalling mechanisms.
Depressor responses to nicotine microinjected into the NTS of Wistar-Kyoto rats were elicited in the absence and presence of an antagonist of α7 nAChR, the calcium chelator ethylene glycol tetraacetic acid, a calmodulin-specific inhibitor, nitric oxide (NO) synthase (NOS) inhibitor, endothelial NOS (eNOS)-selective inhibitor or neuronal NOS (nNOS)-specific inhibitor.
Microinjection of nicotine into the NTS produced a dose-dependent decrease in BP and HR, and increased nitrate levels. This depressor effect of nicotine was attenuated after pretreatment with a nAChR antagonist or blockers of the calmodulin-eNOS pathway. In contrast, N5-(1-Imino-3-butenyl)-L-ornithine (vinyl-L-NIO), nNOS-specific inhibitor, did not diminish these nicotine-mediated effects. Calmodulin was found to bind eNOS after nicotine injection into NTS. However, nicotine did not affect the eNOS phosphorylation level or eNOS upstream extracellular signal-regulated kinases (ERK)1/2 and Akt phosphorylation levels. Furthermore, pretreatment with an ERK1/2 or Akt inhibitor did not attenuate nicotine-induced depressor effects in the NTS.
These results suggest that the nAChR-Ca(2+) -calmodulin-eNOS-NO signalling pathway, but not nNOS, plays a significant role in central BP regulation, and neither the ERK1/2 nor Akt signalling pathway are significantly involved in the activation of eNOS by nAChRs in the NTS.
British Journal of Pharmacology 07/2011; 163(6):1203-13. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to examine the roles of adherence attitude to antidepressants and patient education as mediators in mediating patients' attitudes toward antidepressant use.
A sample of 201 outpatients, 50 years of age or older, with major depressive disorder, completed a drug use questionnaire, attitudes toward and patient education about antidepressants questionnaire, and Adherence Attitude Inventory.
Attitudes toward antidepressants were positively associated to antidepressant use, an association explained by the mediating variable, patient education about antidepressants. Adherence attitudes to antidepressants were a mediator that accounted to a significant degree for the causal relationship between attitudes toward antidepressants and antidepressant use.
Adequate patient education and an understanding of patients' adherence attitude to antidepressant use are needed in nursing practice to reduce patients' uncertainty about treatment and increase successful treatment.
Perspectives In Psychiatric Care 06/2010; 47(1):13-22. · 1.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate patients' attitudes toward complementary and alternative medicine, the education nurses provided about complementary and alternative medicine for treating depression and to test whether such education mediates the effect of complementary and alternative medicine use and attitudes toward complementary and alternative medicine.
Although we know that attitudes influence behaviour, very few studies simultaneously explore the relationship between attitudes, education and complementary and alternative medicine use.
This study was conducted as part of a larger survey, using face-to-face survey interviews with 206 adult patients aged 50 years or over and hospitalised in conventional hospitals in Taiwan for treatment of depression. The attitudes toward complementary and alternative medicine and patient education about complementary and alternative medicine instruments were specially developed for the study.
Participants expressed slightly favourable attitudes toward complementary and alternative medicine. Many participants (50%) expressed that they were willing to try any potential treatment for depression. They believed that complementary and alternative medicine helped them to feel better and to live a happier life. However, 66.5% of participants reported that they had inadequate knowledge of complementary and alternative medicine. Participants with a higher monthly income, longer depression duration and religious beliefs hold more positive attitudes toward complementary and alternative medicine. Most participants were not satisfied with the education they received about complementary and alternative medicine. Patient education about complementary and alternative medicine was found to be a mediator for the use of complementary and alternative medicine.
Patient education from nurses may predict patients' attitudes toward complementary and alternative medicine. Continuing nursing education is needed to enable nurses to respond knowledgeably to concerns patients may have about complementary and alternative medicine and treatment options.
This study highlights the potential role of patient education about complementary and alternative medicine as an effective way of adjusting patients' attitudes toward complementary and alternative medicine and to link both patients' preferences for complementary and alternative medicine and health professionals' concerns about the proper use of complementary and alternative medicine for depression management and adverse drug interactions.
Journal of Clinical Nursing 04/2010; 19(7-8):988-97. · 1.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this prospective, controlled study was to evaluate the risk factors for postoperative emesis in patients undergoing gynecologic surgery and receiving patient-controlled analgesia for three days.
Six hundred twenty-five gynecologic patients with an American Society of Anesthesiologists physical status of I to III undergoing lower-abdominal surgeries were enrolled. A standard, general anesthetic technique was used. Postoperative pain was treated by a patient-controlled analgesia device with bolus intravenous doses of 1 mg morphine. For 3 days after surgery patients were assessed for occurrence of emesis, sedation, and pain intensity when at rest and during movement.
The incidence of emesis was 26% on postoperative day 1, 13% on day 2, and 4% on day 3. On all 3 days, patients' pain scores when at rest and when coughing were higher for those with emesis than for those without. During the first 2 postoperative days the patients with and those without emesis consumed similar amounts of morphine daily, but on the third day the patients with emesis consumed significantly more morphine than did those without emesis ( <0.05). Further logistic regression analysis showed that incident pain was the main risk factor for postoperative emesis on all 3 days.
The results suggested that postoperative pain was an associative risk factor to increase the incidence of emesis in these female patients.
Clinical Journal of Pain 18(5):317-23. · 2.55 Impact Factor