Comparison of Inotropic and Chronotropic Responses in Rat Isolated Atria and Ventricles

Brown, Lindsay; Sernia, Conrad; Newling, Ross; Fletcher, Peter

doi:10.1111/j.1440-1681.1991.tb01393.x

Cited by 12 publications

(10 citation statements)

References 21 publications

(23 reference statements)

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“…Left atrial responses are often used for investigation of positive inotropic compounds (Bohm et al 1989), although atrial responses may not mimic ventricular responses (Brown et al 1991). This has been confirmed in the present study where BDF 9148 produced negative inotropy in left atria but positive inotropy in ventricular muscles from hyperthyroid rats.…”

supporting

confidence: 85%

“…The heart was rapidly removed after chloroform euthanasia and the left atrium and left ventricular papillary muscles were dissected free and prepared for measurement of force of contraction (Brown et al 1991). Tissues were suspended in organ baths at a resting tension of 5-10mN adjusted to give the maximal twitch response.…”

Section: Isolated Contracting Cardiac Tissuesmentioning

confidence: 99%

“…The rat heart has been shown to be useful in testing positive inotropic compounds (Bohm et al 1989;Brown et al 1991). Specific disease-induced changes in isolated rat heart tissues in the positive inotropic responses to P-adrenoceptor agonists have been reported: hyperthyroidism increased potency but decreased maximal increase in force ; potency was decreased in hypothyroidism (Brown et al 1994a) and in genetically hypertensive rats (Bohm et al 1988); ventricular responses to noradrenaline were markedly increased in dwarf rats .…”

Section: Introductionmentioning

confidence: 99%

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Positive Inotropic Responses of the Sodium Channel Modulator BDF 9148 in Diseased Rat Myocardium

Hoey

Nankervis

Brown

1995

Clin Exp Pharma Physio

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1. This study has defined the positive inotropic responses to the sodium channel modulator BDF 9148 in rats with hypertension, thyroid dysfunction, diabetes or dwarfism. Concentration-response curves to BDF 9148 and calcium chloride were determined in isolated left atria and left ventricular papillary muscles. 2. BDF 9148 increased force of contraction in left ventricular papillary muscles in all disease states with maximal responses comparable to calcium chloride. BDF 9148 potency was significantly decreased in muscles from diabetic rats only. 3. BDF 9148 produced similar responses in left atria except from hyperthyroid rats where negative inotropic responses only were measured. This exception confirms that the left atria is an imperfect model for ventricular responsiveness. 4. Thus, the increase in force of contraction in the ventricles as a consequence of sodium channel modulation by BDF 9148 is maintained in these disease states unlike responses to alpha-or beta-adrenoceptor agonists.

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supporting

confidence: 85%

Section: Isolated Contracting Cardiac Tissuesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Positive Inotropic Responses of the Sodium Channel Modulator BDF 9148 in Diseased Rat Myocardium

Hoey

Nankervis

Brown

1995

Clin Exp Pharma Physio

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“…The right atria and papillary muscles from the left ventricle were removed and suspended in organ baths at a resting tension of 5 – 10 mN adjusted to give the maximal twitch response. Tissues were bathed in a modified Tyrodes solution (in m M ): NaCl 136.9, KCl 5.4, MgCl 2 1.05, CaCl 2 1.8, NaHCO 3 22.6, NaH 2 PO 4 0.42, glucose 5.5, ascorbic acid 0.28, sodium edetate 0.05, bubbled with 95%O 2 /5%CO 2 and stimulated at 1 Hz at 35°C as previously described (Brown et al ., 1991b). Cumulative concentration‐response curves were measured for noradrenaline and, following washout and re‐equilibration, to calcium chloride.…”

Section: Methodsmentioning

confidence: 99%

Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA‐salt hypertensive rats

Mirkovic

Seymour

Fenning

et al. 2002

British J Pharmacology

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118

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1 This study has administered pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) or amiloride to attenuate the remodelling and associated functional changes, especially an increased cardiac stiness, in DOCA-salt hypertensive rats. body wt) without lowering systolic blood pressure. 4 Collagen deposition was signi®cantly increased in the interstitium after 2 weeks and further increased with scarring of the left ventricle after 4 weeks; pirfenidone and amiloride reversed the increases and prevented further increases. This accumulation of collagen was accompanied by an increase in diastolic stiness constant; both amiloride and pirfenidone reversed this increase. 5 Noradrenaline potency (positive chronotropy) was decreased in right atria (neg log EC50: control 6.92+0.06; DOCA-salt 6.64+0.08); pirfenidone but not amiloride reversed this change. Noradrenaline was a more potent vasoconstrictor in thoracic aortic rings (neg log EC50: control 6.91+0.10; DOCA-salt 7.90+0.07); pirfenidone treatment did not change noradrenaline potency. 6 Thus, pirfenidone and amiloride reverse and prevent cardiac remodelling and the increased cardiac stiness without reversing the increased vascular responses to noradrenaline. British Journal of Pharmacology (2002) 135, 961 ± 968

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“…They can be distinguished on the basis of contractile properties, rhythm generation, and response to neurohumoral stimulation (Brown et al, 1991;Barth et al, 2005;Narolska et al, 2005). Contractile activity of the heart ensures that blood flow is adapted to the needs of the organism.…”

mentioning

confidence: 99%

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

Moore-Morris¹,

Varrault²,

Mangoni³

et al. 2009

Mol Pharmacol

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Cardiac function is regulated by many hormones and neurotransmitters that exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Identification of new GPCRs that might display a specific pattern of expression within the heart and differentially regulate specific cardiac functions represents an important issue for the development of new drugs. Indeed, highly targeted receptors represent only a small percentage of known GPCRs. Here, we quantified the expression of 395 endoGPCRs (all GPCRs excluding taste and odorant receptors) in male mouse right and left atria and ventricles by using high-throughput real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and focused on the 135 most highly expressed transcripts. No cardiac functional data are available for almost half of these receptors; therefore, linking GPCR expression patterns to cardiac function has allowed us to provide new insights into the possible function of some of these receptors. Indeed, ventricles and atria are both contractile; however, the latter, and especially the right atrium, are central to the generation and regulation of cardiac rhythm. Accordingly, the right atrium exhibited the most specific signature, whereas the majority of GPCRs found in ventricles were evenly expressed in both the right and left chambers. RT-PCR data were confirmed at the protein level for six selected transcripts. Furthermore, we provide new data showing that, as suggested by our repertoire, the metabotropic glutamate receptor 1b is expressed and is functional in ventricular cardiac myocytes. This is the first report describing GPCRs in the four cardiac chambers and may assist in the identification of therapeutic targets.The four cardiac chambers display morphological and functional differences. They can be distinguished on the basis of contractile properties, rhythm generation, and response to neurohumoral stimulation (Brown et al., 1991;Barth et al., 2005;Narolska et al., 2005). Contractile activity of the heart ensures that blood flow is adapted to the needs of the organism. Left ventricular performance depends on the chamber's capacity to fill up (diastolic property) and to empty (systolic property), and these properties are altered in pathological conditions, the final consequence being heart failure. To trigger the contractile activity, cardiac automaticity is generated by a set of specialized pacemaker cells forming the sinoatrial node (SAN) (Mangoni and Nargeot, 2008). Compared with myocytes of the working myocardium, pacemaker SAN cells are devoted to the generation of an electrical oscillation rather than having a contractile activity. At the molecular level, heart chamber heterogeneity is reflected by the expression patterns of different sets of genes such as transcription factors (Tabibiazar et al., 2003) and ion channels (Marionneau et al., 2005). The heart expresses GPCRs (Regard et al.,

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Comparison of Inotropic and Chronotropic Responses in Rat Isolated Atria and Ventricles

Cited by 12 publications

References 21 publications

Positive Inotropic Responses of the Sodium Channel Modulator BDF 9148 in Diseased Rat Myocardium

Positive Inotropic Responses of the Sodium Channel Modulator BDF 9148 in Diseased Rat Myocardium

Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA‐salt hypertensive rats

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

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