Receptor systems in the non-failing human heart

Brodde, Otto‐Erich; Broede, Andrea; Daul, A; Kunde, K.; Michel, Martin C.

doi:10.1007/978-3-642-72474-9_1

Cited by 22 publications

(23 citation statements)

References 44 publications

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“…These results suggest that either atropine dosage was not sufficiently high to block the increase in vagal tone following a hypertensive stimulus or that an ␣-AR component of the action of epinephrine has negative chronotropic effects. The failure to demonstrate significant chronotropic or inotropic effects of agents such as histamine or serotonin, despite their ability to stimulate cardiac adenylate cyclase in vitro (39,40), suggests that ␤-ARs are the primary G-protein-coupled receptors regulating cardiac function in vivo.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and Metabolic Alterations in Mice Lacking Both β1- and β2-Adrenergic Receptors

Rohrer¹,

Chruscinski

Schauble

et al. 1999

Journal of Biological Chemistry

259

185

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The activation state of ␤-adrenergic receptors (␤-ARs) in vivo is an important determinant of hemodynamic status, cardiac performance, and metabolic rate. In order to achieve homeostasis in vivo, the cellular signals generated by ␤-AR activation are integrated with signals from a number of other distinct receptors and signaling pathways. We have utilized genetic knockout models to test directly the role of ␤1-and/or ␤2-AR expression on these homeostatic control mechanisms. Despite total absence of ␤1-and ␤2-ARs, the predominant cardiovascular ␤-adrenergic subtypes, basal heart rate, blood pressure, and metabolic rate do not differ from wild type controls. However, stimulation of ␤-AR function by ␤-AR agonists or exercise reveals significant impairments in chronotropic range, vascular reactivity, and metabolic rate. Surprisingly, the blunted chronotropic and metabolic response to exercise seen in ␤1/ ␤2-AR double knockouts fails to impact maximal exercise capacity. Integrating the results from single ␤1-and ␤2-AR knockouts as well as the ␤1-/␤2-AR double knockout suggest that in the mouse, ␤-AR stimulation of cardiac inotropy and chronotropy is mediated almost exclusively by the ␤1-AR, whereas vascular relaxation and metabolic rate are controlled by all three ␤-ARs (␤1-, ␤2-, and ␤3-AR). Compensatory alterations in cardiac muscarinic receptor density and vascular ␤3-AR responsiveness are also observed in ␤1-/␤2-AR double knockouts. In addition to its ability to define ␤-AR subtype-specific functions, this genetic approach is also useful in identifying adaptive alterations that serve to maintain critical physiological setpoints such as heart rate, blood pressure, and metabolic rate when cellular signaling mechanisms are perturbed.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular and Metabolic Alterations in Mice Lacking Both β1- and β2-Adrenergic Receptors

Rohrer¹,

Chruscinski

Schauble

et al. 1999

Journal of Biological Chemistry

259

185

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“…Noradrenaline is known to mediate its positive inotropic effect mainly via b 1 -adrenoceptors to evoke maximum positive inotropic effects in both atria and ventricles (Brodde et al 1992), but also a 1 -adrenoceptors have been demonstrated to contribute with a positive inotropic effect (Bohm et al 1988;Endoh et al 1991). If the maximum responses to noradrenaline are taken as an approximation of maximum positive inotropic responses, then our results would suggest a higher potential for modulation of contractile force in atrial than in ventricular tissue.…”

Section: Discussionmentioning

confidence: 68%

Modulation of Contractile Force by Endothelin Receptors in Porcine Myocardial Trabeculae

Opgaard¹,

Tom²,

Vries³

et al. 2000

Pharmacology & Toxicology

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The aim of the study was to determine possible inotropic effects mediated by endothelin-A and endothelin-B receptors in porcine myocardial trabeculae from right atria and left ventricles. Isolated trabeculae were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Endothelin-1 and endothelin-3 had a strong and potent positive inotropic effect in all trabeculae. In all atrial and in some ventricular trabeculae this effect was preceded by a transient negative inotropic effect at 10 ª7 M. The endothelin-B receptor agonist IRL 1620 had a positive inotropic effect in some of the ventricular trabeculae, and no negative inotropic effect. Another endothelin-B receptor agonist, sarafotoxin S6c, had no positive inotropic effect, but induced a transient negative inotropic effect in some atrial trabeculae at 10 ª7 M. In atrial trabeculae the preincubation with the endothelin-A receptor antagonist FR139317 (10 ª6 M) decreased significantly (PϽ0.01) the maximum positive inotropic responses and abolished negative inotropic responses to endothelin-1. In conclusion, both endothelin-A and endothelin-B receptors may have the potential to mediate both positive and negative inotropic responses, but a positive inotropic effect mediated mainly via endothelin-A receptors seems to predominate.

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“…Being Mcholinoreceptors, the receptors to SS are coupled to adenylate cyclase via inhibitory G proteins. In both cases stimulation of the receptors decreases intracellular cAMP content [11]. Taken together, these functional features are also characteristic of 5-opiate receptors through which the cardiotropic effects of enkephalins are predominantly mediated I2,9,13].…”

Section: Resultsmentioning

confidence: 98%

Specificity of vagotropic peptide action under subtotal blockade of cardiac M-cholinoreceptors

Osadchii

Pokrovskii

1998

Bull Exp Biol Med

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In experiments on anesthetized cats modulation of the components of vagal chronotropic effects by somatostatin and Met-enkephalin is studied under complete block of Mcholinoreceptors caused by administration of the M2-cholinoblocker Imperialine or the subthreshold doses of the non-selective M-cholinolytic agent methacine. A differential character of vagotropic effect of peptides is revealed, which is manifested in restoration of the synchronizing vagal component that was decreased by cholinolytics, while a similar effect on the inhibitory tonic vagal influence was absent.

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Receptor systems in the non-failing human heart

Cited by 22 publications

References 44 publications

Cardiovascular and Metabolic Alterations in Mice Lacking Both β1- and β2-Adrenergic Receptors

Cardiovascular and Metabolic Alterations in Mice Lacking Both β1- and β2-Adrenergic Receptors

Modulation of Contractile Force by Endothelin Receptors in Porcine Myocardial Trabeculae

Specificity of vagotropic peptide action under subtotal blockade of cardiac M-cholinoreceptors

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