Agonist-specific activation of the beta2-adrenoceptor/Gs-protein and beta2-adrenoceptor/Gi-protein pathway in adult rat ventricular cardiomyocytes.

In rat ventricular cardiomyocytes beta2-adrenoceptors (AR) couple to Gs- and Gi-protein, and evidence has accumulated that beta2-AR agonists can differentially activate either Gs- or Gs- and Gi-protein. In this study, in isolated adult rat ventricular cardiomyocytes, we assessed the effects of pertussis toxin (PTX) on beta2-AR agonist (terbutaline (TER), salbutamol (SAL) and fenoterol (FEN)) evoked inhibition of phenylephrine (PE)-induced increase in the rate of protein synthesis (assessed as [3H]phenylalanine incorporation) to find out which beta2-AR agonist activates selectively Gs- or Gs- and Gi-protein. PE (1 microM) increased the rate of protein synthesis from 100% to 130+/-2% (n = 34).

Role of beta 1- and beta 2-adrenoceptors in hypertrophic and apoptotic effects of noradrenaline and adrenaline in adult rat ventricular cardiomyocytes.

In adult rat ventricular cardiomyocytes alpha1-adrenoceptor (AR) stimulation causes increases in protein synthesis. On the other hand beta1-AR stimulation inhibits protein synthesis, and evokes apoptotic cell death. We studied, in adult rat ventricular cardiomyocytes, effects of noradrenaline (NA), adrenaline (ADR) and phenylephrine (PE) on protein synthesis (assessed by [3H]-phenylalanine incorporation into the cardiomyocytes) in relation to effects on early apoptosis (measured by Annexin V/propidium iodide staining).

Cardiac beta-adrenoceptor changes in monocrotaline-treated rats: differences between membrane preparations from whole ventricles and isolated ventricular cardiomyocytes.

In monocrotaline (MCT)-treated rats the beta-adrenoceptor-G-protein-adenylyl cyclase system-determined in crude membrane preparations from whole ventricular tissue-was desensitized not only in right (RV) but also in left ventricles (LV). This study aimed to assess the specific contribution of cardiomyocytes to these beta-adrenoceptor changes. Six-week-old male Wistar rats were treated with 60 mg/kg body weight MCT intraperitoneally; within 4-6 weeks, rats developed marked RV hypertrophy.

Demonstration of functional M3-muscarinic receptors in ventricular cardiomyocytes of adult rats.

1 Muscarinic receptors (M-receptors) in the mammalian heart are predominantly of the M(2)-subtype. The aim of this study was to find out whether there might exist an additional myocardial non-M(2)-receptor. 2 For this purpose, we assessed, in adult rat isolated ventricular cardiomyocytes, carbachol-induced [(3)H]-inositol phosphate (IP) formation, and its inhibition by M-receptor antagonists.

Ventricular hypertrophy plus neurohumoral activation is necessary to alter the cardiac beta-adrenoceptor system in experimental heart failure.

Treatment of rats with monocrotaline (MCT) leads to pulmonary hypertension, right ventricular (RV) hypertrophy, and finally to RV heart failure. This is associated with characteristic changes in right ventricular beta-adrenoceptors (beta-AR), neuronal noradrenaline transporter (NAT) density and activity (uptake1), and G protein-coupled receptor kinase (GRK) activity. This study aimed to find out factors that determine beta-AR, uptake1, and GRK changes.

The ageing heart: influence of cellular and tissue ageing on total content and distribution of the variants of elongation factor-2.

The involvement of elongation factor-2 (EEF-2), a key-protein of peptide-chain elongation, in the slowing down of protein synthesis during cardiac ageing was addressed. EEF-2 was measured in rat heart extracts and isolated rat cardiomyocytes (CM) from newborn and adult rats using sodium-dodecylsulphate polyacrylamide gel electrophoresis after specific labeling with [32P]ADP-ribosylation or immunoblot. The age-dependent proportional content of several eucaryotic elongation factor-2 (eEF-2) subtypes in rat CM and rat heart extracts was compared using one-dimensional isoelectric focusing.

Differential effects of bucindolol and carvedilol on noradenaline-induced hypertrophic response in ventricular cardiomyocytes of adult rats.

In adult rat ventricular cardiomyocytes, noradrenaline exerts dual effects on protein synthesis: increases via alpha(1)-adrenoceptors and decreases via beta(1)-adrenoceptors. Carvedilol and bucindolol are beta-blockers with additional alpha(1)-adrenoceptor blocking activities. We studied the effects of carvedilol and bucindolol on noradrenaline-induced protein synthesis (assessed by [(3)H]phenylalanine incorporation) in adult rat ventricular cardiomyocytes.

Changes in alpha(1)-adrenergic vascular reactivity in monocrotaline-treated rats.

In rats, injection of monocrotaline (MCT) causes pulmonary hypertension that leads to right ventricular failure. The aim of the present study was to characterize the responses of various vessels (the pulmonary artery, the thoracic aorta and small mesenteric arteries) to noradrenaline (NA; 10(-10)-10(-5) M) and carbachol (10 microM) in MCT-treated rats. For this purpose 6-week-old male Wistar rats ( n=13) were treated with 60 mg/kg MCT i.

Cardiac beta-adrenoceptor desensitization due to increased beta-adrenoceptor kinase activity in chronic uremia.

Patients with chronic renal failure develop an autonomic dysfunction with impaired baroreflex control and attenuated cardiovascular beta-adrenoceptor response to noradrenaline. In rats that underwent 5/6-nephrectomy (SNX), cardiac beta-adrenoceptor responsiveness was reduced as well. Therefore, the aim of this study was to further investigate the mechanism underlying cardiac beta-adrenoceptor desensitization in SNX rats.