Impaired coronary function in Wistar Ottawa Karlsburg W rats—a new model of the metabolic syndrome

Grisk, Olaf; Frauendorf, Tillmann; Schlüter, Torsten; Klöting, Ingrid; Kuttler, Beate; Krebs, Alexander; Lüdemann, Jan; Rettig, Rainer

doi:10.1007/s00424-007-0267-6

Cited by 18 publications

(10 citation statements)

References 32 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent findings from Grisk et al who documented that α 1 -adrenoceptor mediated vasoconstriction is enhanced in isolated coronaries from Wistar Ottawa Karlsburg W rats [104], are consistent with in vivo data from our laboratory which demonstrated increased coronary constriction to the α 1 -adrenoceptor agonist methoxamine in MetS dogs (Fig. 3A) [42].…”

Section: Neurohumoral Modulation Of Coronary Flow In Metssupporting

confidence: 87%

“…Decreased vasodilation to the β-agonist isoproterenol has also been observed in isolated coronary arterioles [104]. However, the extent to which altered sympathetic β-adrenoceptor expression and/or signaling contribute to coronary vascular dysfunction in MetS in vivo has not been investigated.…”

Section: Neurohumoral Modulation Of Coronary Flow In Metsmentioning

confidence: 99%

Heart of the matter: Coronary dysfunction in metabolic syndrome

Berwick¹,

Dick²,

Tune³

2012

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

Metabolic syndrome (MetS) is a collection of risk factors including obesity, dyslipidemia, insulin resistance/impaired glucose tolerance, and/or hypertension. The incidence of obesity has reached pandemic levels, as ~20–30% of adults in most developed countries can be classified as having MetS. This increased prevalence of MetS is critical as it is associated with a two-fold elevated risk for cardiovascular disease. Although the pathophysiology underlying this increase in disease has not been clearly defined, recent evidence indicates that alterations in the control of coronary blood flow could play an important role. The purpose of this review is to highlight current understanding of the effects of MetS on regulation of coronary blood flow and to outline the potential mechanisms involved. In particular, the role of neurohumoral modulation via sympathetic α-adrenoceptors and the renin-angiotensin-aldosterone system (RAAS) are explored. Alterations in the contribution of end-effector K+, Ca2+, and transient receptor potential (TRP) channels are also addressed. Finally, future perspectives and potential therapeutic targeting of the microcirculation in MetS are discussed.

show abstract

“…Genomic scan studies have revealed a linkage of the MS and/or diabetes to a region on chromosome 3 (3q26-27), where the gene encoding adiponectin, apM1, is located [28]. One important clinical characteristic displayed by these animals was the impaired coronary function, due to increased alpha(1)-adrenoceptor-mediated coronary constriction (at 3 and 10 months of age), and to a seriously blunted beta-adrenoceptor-mediated coronary relaxation (at 16 months of age) [29]. …”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Changes in Animal Models of Metabolic Syndrome

Lehnen

Rodrigues

Irigoyen

et al. 2013

Journal of Diabetes Research

View full text Add to dashboard Cite

Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.

show abstract

“…b-Adrenoceptor-mediated vasodilatation is impaired in diseases such as hypertension and type 2 diabetes (Naslund et al, 1990;Harada et al, 1999;Chen and Doggrell, 2002;Grisk et al, 2007). As ERK activity is enhanced in vascular smooth muscle in these diseases (Touyz et al, 2002;Kim et al, 2005;Matsumoto et al, 2006), the data presented here open up the possibility that the impairment of b-adrenoceptor function is due in part to the increased ERK activity.…”

Section: Discussionmentioning

confidence: 65%

Effect of inhibition of extracellular signal‐regulated kinase on relaxations to β‐adrenoceptor agonists in porcine isolated blood vessels

Uhiara

Alexander

Roberts

2009

British J Pharmacology

View full text Add to dashboard Cite

Background and purpose: Stimulation of vascular b-adrenoceptors causes vasodilatation through activation of adenylyl cyclase (AC) and plasma membrane potassium channels, and b-adrenoceptors have been linked to activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase in various cell lines. However, how these findings relate to functional responses in intact tissues is largely unknown. The aim of this study, therefore, was to investigate the role of ERK in b-adrenoceptor-induced vasodilatation. Experimental approach: Segments of porcine coronary artery were mounted in a Mulvany wire myograph and bathed in Krebs-Henseleit buffer gassed with 95% O2/5% CO2 and maintained at 37°C. Tissues were pre-contracted with the thromboxane mimetic U46619, endothelin-1 or KCl. Cumulative concentration-response curves to b-adrenoceptor agonists or forskolin were then carried out in the absence or presence of the mitogen-activated protein kinase kinase (MEK) inhibitors PD98059 (10 or 50 mM) or U0126 (10 mM). Key results: PD98059 caused a concentration-dependent leftward shift in response to isoprenaline (pEC50 control, 7.5 Ϯ 0.1; 50 mM PD98059, 8.1 Ϯ 0.1: P < 0.05). Inhibition of MEK also enhanced the maximum relaxation seen with salbutamol, but not the responses to the b1-adrenoceptor selective agonist xamoterol or the AC activator forskolin. There was no enhancement of the relaxations to b-adrenoceptor agonists after inhibition of ERK activation in tissues pre-contracted with KCl or treated with the K + channel blocker tetraethylammonium. Conclusions and implications:These data indicate that ERK inhibits b2-adrenoceptor-mediated vasodilatation through a mechanism which may involve inactivation of plasma membrane potassium channels.

show abstract

“…A more realistic model was developed in 2007 by Kovacs et al The Wistar Ottawa Karlsburg W (WOKW) rats, like other models, exhibit the key features of MetS but have a polygenic background that makes the model more applicable to human disease (Kovacs et al, 2000). Recently, the WOKW rats have been used to identify quantitative trait loci for several of the major traits of MetS, as well as to establish an association between MetS and impaired coronary function (Grisk et al, 2007).…”

Section: Animal Models Of Metabolic Syndromementioning

confidence: 99%