Existence of beta(3)-adrenoceptors in rat heart: functional implications.

1. beta(3)-Adrenoceptors (AR) have been reported to be present in numerous species, where they mediate multiple responses. 2. The aim of the present study was to determine whether beta(3)-AR are present in intact rat heart and the functional implications of beta(3)-AR stimulation. The response to the cardiac beta(3)-AR-selective agonist BRL37344 was expressed as the percentage of values measured at baseline. 3. BRL37344 induced dose-dependent negative inotropic effects at concentrations ranging from 10(-11) to 10(-7) mol/L. BRL37344 (10(-8) mol/L) induced a decrease of left ventricular developed pressure (LVDP) from 127 +/- 5 to 89 +/- 16 mmHg (69 +/- 15%; P < 0.01) and +dP/dt from 2594 +/- 59 to 1885 +/- 50 mmHg/s (72 +/- 8%; P < 0.01). Moreover, a significant reduction of -dP/dt from 2176 +/- 42 to 1458 +/- 43 mmHg/s (67 +/- 8%; P < 0.01) was observed. The BRL37344 dose-response curves were not altered by nadolol (10(-5) mol/L), a potent beta(1)- and beta(2)-AR antagonist, but were completely suppressed by the addition of SR59230A (10(-5) mol/L), a potent beta(3)-AR antagonist. 4. The present study provides functional evidence for the presence of beta(3)-AR in rat hearts and shows, for the first time, that a highly specific beta(3)-AR antagonist can block the attenuation of LVDP caused by the specific beta(3)-AR agonist BRL37344 in rat beating hearts.

Alterations of beta3-adrenoceptors expression and their myocardial functional effects in physiological model of chronic exercise-induced cardiac hypertrophy.

Physical training induces cardiovascular autonomic nervous system regulation adaptations, which could result from beta adrenergic receptor (AR) modifications. Among them, beta(3 )AR alterations have been recently reported but their functional effect remained to discuss. To explain the beta(3) AR gene expression in relation to function, we simultaneously studied the left ventricle (LV) beta(3) AR mRNA and protein levels and the myocardial functional effects of a beta(3) AR agonist following physical training. Forty rats were assigned to either a control (C; N = 20) or a trained (T; N = 20) group. The treadmill running protocol was performed for 8 weeks. Histological measurements on LV slices were quantified. The beta(3) AR mRNA abundance was studied with RT-PCR and beta(3) AR protein density with Western-Blot analysis. Myocardial functional effects of a beta(3) AR agonist, BRL37344 (10(-8) M), were studied in Langendorff-perfused hearts. Histological data confirmed the adapted patterns of the physiological cardiac hypertrophy observed in T (P < 0.01), with a significant increase in arteries density (P < 0.01) and an unchanged collagen concentration. The beta(3) AR protein density was increased in T (154 +/- 38% in T vs. 100 +/- 24% in C; P < 0.05), but no change was noted concerning the beta(3) AR mRNA level. After BRL37344 perfusion LVDP, +dP/dT and -dP/dT, in C (P < 0.01), and only +dP/dT in T (P < 0.05) were decreased. Moreover, all LV hemodynamic parameters were more altered after BRL37344 in C than in T (P < 0.01).Thus, in this physiological model of cardiac hypertrophy, an increase of beta(3) AR density without beta(3) AR mRNA alteration was observed. Classical negative myocardial lusitropic and inotropic effects induced by a specific agonist of beta(3) AR were diminished in trained rats.

Changes in blood lipid peroxidation markers and antioxidants after a single sprint anaerobic exercise.

It has been well demonstrated that the principal factor responsible for oxidative damage during exercise is the increase in oxygen consumption. However, other theoretical factors (acidosis, catecholamine autoxidation, ischemia-reperfusion syndrome, etc.) that are known to induce, in vitro, oxidative damage may also be operative during short-term supramaximal anaerobic exercise. Therefore, we hypothesized that short-term supramaximal anaerobic exercise (30-s Wingate test) could induce an oxidative stress. Lipid peroxidation markers [serum lipid radical production detected by electron spin resonance (ESR) spectroscopy and plasma malondialdehyde (MDA) levels detected by the thiobarbituric acid reactive substances (TBARS) method], as well as erythrocyte antioxidant enzyme activities [glutathione peroxidase (GPx), superoxide dismutase (SOD)] and erythrocyte glutathione (GSH) levels, were measured at rest, after the Wingate test and during the 40 min of recovery. The recovery of exercise was associated with a significant increase (x2.7) in lipid radical production detected by ESR spectroscopy, as well as with changes in the erythrocyte GSH level (-13.6%) and SOD activity (-11.7%). The paradoxical decrease in plasma TBARS (-23.7%) which was correlated with the peak power developed during the Wingate test ( r=-0.7), strongly suggests that such exercise stimulates the elimination of MDA. In conclusion, this study demonstrates that short-term supramaximal anaerobic exercise induces an oxidative stress and that the plasma TBARS level is not a suitable marker during this type of exercise.

Effect of endurance training on oestrogen receptor alpha transcripts in rat skeletal muscle.

Endurance training induces, in female rats, alterations of oestrous cycle with decrease in plasma oestradiol levels. Moreover, it is well known that oestradiol concentrations modify oestrogen receptor levels. In order to further explain the effects of oestrogens on skeletal muscles, we hypothesized that endurance training modifies the levels of oestrogen receptor alpha messenger ribonucleic acid (ER alpha mRNA) in rat gastrocnemius muscle. Wistar rats were separated into four groups: male controls (C(m)) (n=7), female controls (C(f)) (n=6), male trained (E(m)) (n=7) and female trained (E(f)) (n=6). The endurance training programme was performed for 7 weeks, 5 days week-1 and consisted of 1 h of continuous running on an adapted motor-driven treadmill. At the end of the training session, the gastrocnemius muscle was isolated, weighed and semiquantification of ER alpha mRNA was performed using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. The citrate synthase (CS) activity of the gastrocnemius muscle was measured by a fluorimetric method. The CS activity of the male and female gastrocnemius muscle, respectively, 100 +/- 7% in C(m) (n=7) vs. 120 +/- 14% in E(m) (n=6, P < 0.01) and 100 +/- 13% in C(f) (n=6) vs. 138 +/- 23% in E(f) (n=6, P < 0.01) was significantly increased after 7 weeks of training. The ER alpha mRNA levels were significantly increased in E(f) compared with C(f) (0.49 +/- 0.15 vs. 0.31 +/- 0.11, P < 0.01) but not in E(m) compared with C(m) (0.37 +/- 0.15 vs. 0.37 +/- 0.13). In conclusion, these results demonstrate that 7 weeks of endurance training increased the level of transcripts encoding ER alpha in rats with the increase restricted to the females.