2 research outputs found
Diverse Regulation of Cardiac Expression of Relaxin Receptor by alpha(1)- and beta(1)-Adrenoceptors
No full textRelaxin, a new drug for heart failure therapy, exerts its cardiac actions through relaxin family peptide receptor 1 (RXFP1). Factors regulating RXFP1 expression remain unknown. We have investigated effects of activation of adrenoceptors (AR), an important modulator in the development and prognosis of heart failure, on expression of RXFP1 in rat cardiomyocytes and mouse left ventricles (LV). Expression of RXFP1 at mRNA (real-time PCR) and protein levels (immunoblotting) was measured in cardiomyocytes treated with alpha- and beta-AR agonists or antagonists. RXFP1 expression was also determined in the LV of transgenic mouse strains with cardiac-restricted overexpression of alpha(1A)-, alpha(1B)- or beta(2)-AR. Specific inhibitors were used to explore signal pathways involved in alpha(1)-AR mediated regulation of RXFP1 in cardiomyocytes. In cultured cardiomyocytes, alpha(1)-AR stimulation resulted in 2-3 fold increase in RXFP1 mRNA (P < 0.001), which was blocked by specific inhibitors for protein kinase C (PKC) or mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK). Activation of beta(1)-, but not beta(2)-AR, significantly inhibited RXFP1 expression (P < 0.001). Relative to respective wild-type controls, RXFP1 mRNA levels in the LV of mice overexpressing alpha(1A)- or alpha(1B)-AR were increased by 3- or 10-fold, respectively, but unchanged in beta(2)-AR transgenic hearts. Upregulation by alpha(1)-AR stimulation RXFP1 expression was confirmed at protein levels both in vitro and in vivo. Expression of RXFP1 was up-regulated by alpha(1)-AR but suppressed by beta-AR, mainly beta(1)-AR subtype, in cardiomyocytes. Future studies are warranted to characterize the functional significance of such regulation, especially in the setting of heart failure.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000338639900005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cardiac & Cardiovascular SystemsPharmacology & PharmacySCI(E)[email protected]
The GIANT study, a cluster-randomised controlled trial of efficacy of education of doctors about type 2 diabetes mellitus management guidelines in primary care practice
No full textObjectives: Primary aim: does general practitioner (GP) education on type 2 diabetes treatment improve HbA1c? Secondary aim: cardiovascular risk factors, hypoglycaemia, treatment intensification, health service utilisation, treatment barriers. Methods: 99 Asia-Pacific GPs were cluster-randomised to be educated on regional diabetes management guidelines (intervention) or continue standard care (control). The intervention employed meetings, reminders, medical record summary sheets and patient result cards. Each GP recruited four type 2 diabetic patients, assessed at baseline, 6 and 12 months. The primary outcome was mean change in HbA1c from 0 to 6 months in patients with baseline HbA1c >= 6.5%. Results: 361 patients (93%) completed 6 month follow-up. The primary HbA1c outcome was 0.11% (95% CI 0.27, 0.05) with intervention and 0.22% (95% CI 0.39, 0.05) in the control group (p = 0.340). The groups did not differ in control of other glycaemic indices, blood pressure or lipids after 6 or 12 months. In those with HbA1c >= 9.0%, approximately 50% received intensified treatment by 6 months, and 30% in the final 6 months. GPs identified treatment costs and patient reluctance to use insulin as management barriers. Conclusions/interpretation: A structured GP education programme did not improve HbA1c in patients with type 2 diabetes. (C) 2012 Elsevier Ireland Ltd. All rights reserved.Endocrinology & MetabolismSCI(E)3ARTICLE138-459
