Physical training induces cardiovascular autonomic nervous system regulation adaptations, which could result from β adrenergic receptor (AR) modifications. Among them, β3 AR alterations have been recently reported but their functional effect remained to discuss. To explain the β3 AR gene expression in relation to function, we simultaneously studied the left ventricle (LV) β3 AR mRNA and protein levels and the myocardial functional effects of a β3 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 β3 AR mRNA abundance was studied with RT-PCR and β3 AR protein density with Western-Blot analysis. Myocardial functional effects of a β3 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 β3 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 β3 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).

OBJECTIVES:We report in the present study the role of endothelin (ET-1) and ET-1 receptors in the sustained hypoxia-induced systemic hypertension. METHODS:Wistar rats were randomly assigned to live continuously in hypobaric hypoxia (CH rats) or normoxia (N rats). At the end of hypoxic stress exposure (5 weeks at 450 mm Hg), measurements of mean systemic arterial pressure were done. The effects of ET-1 in the presence or not of the endothelium and/or of specific ET-A inhibitors (BQ-123) or ET-B inhibitors (BQ-788), have been investigated in an isolated model of rat thoracic aorta. Finally, plasmatic ET-1 concentrations have been determined by assay procedure. RESULTS:Following five weeks of chronic hypoxic stress, CH rats presented a significant increase of mean systemic arterial pressure (N: 129.1+/-6.8 mm Hg vs CH: 152.5+/-3.4 mm Hg; P<0.05). Despite of this hypoxia-induced hypertension, ET-1 plasmatic concentration was not different between N and CH rats. Finally, CH rats presented a reduce response to ET-1 when compared to N rats. This phenomenon seems to be associated to the ET-A vascular smooth muscle cell receptors, since difference between N and CH rats was still present in endothelium denuded aortic rings in the presence or not of the specific ET-B inhibitors (BQ-788). In addition, in the presence of the specific ET-A inhibitor (BQ-123) response to ET-1 was abolished in N and CH rats to the same extent (N:-98%; CH:-99%). CONCLUSION:This work clearly suggests that, following long term exposure to hypoxia, ET-1 and ET-1 receptors are not involved in the persistence of systemic hypertension in a rat model, and that chronic exposure to severe hypoxic stress was associated with a downregulation of the ET-A receptors response to ET-1.

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.

Chronic physical training may induce morphological and useful functional adaptations which affect all cardiac chambers. Morphological modifications are mainly modest and far from pathologic ones. All these adaptations seem helpful for sport’s performance. Hemodynamic and neurohumoral stresses depend on the muscular exercise type performed, static or dynamic. However, sports-specific adaptive cardiac structural changes are yet debated. Actually, it appears that highly trained athletes develop a left ventricular fair combination of cavity dilatation and increased wall thickness. Thus, it is not possible to clearly separate a strength-trained from an endurance-trained athlete’s heart. However, this review shows that some specific cardiac adaptations mainly linked to the specific training stimulus may be observed. Dilatation slightly predominates in dynamic endurance-trained athletes whereas increased wall thickness slightly predominates in dynamic resistance- and static-trained athletes. Thus, assessment of athletes’ echocardiographic parameters should take into account both sport and training specificities practiced, in terms of quantity and contents.

Endurance training induces cardiovascular adaptations.Alterations in the expression of β adrenoreceptors (β AR) and in M 2 muscarinic receptors (M AchR) have been suggested to be involved in these processes but their understanding is incomplete.The objective of this work was to assess if adaptations linked to endurance training are associated with modifications in mRNA abundance and/or protein levels of different β-AR subtypes and M 2 AchR.At the end of an 8 weeks treadmill protocol, cardiac parameters were evaluated by an electrocardiographic analysis.We measured β AR and M 2 AchR mRNA level (by real-time RT-PCR) and protein density (by western blot).A physiological cardiac hypertrophy (+11%), a bradycardia (P < 0.01) and an increased diastolic function (P < 0.01) were observed in trained rats.The β 3 AR mRNA level remained unchanged in trained as compared to sedentary rats; by contrast, the β 3 AR protein density increased (+54%; P < 0.05).There was no change in β 1 AR mRNA level associated to a non-significant trend towards a decrease of β 1 AR protein level (-26%; P = 0.07) in trained rats.These results also suggest a post-translational regulation of β 1 AR and β 3 AR gene expression.For β 2 AR and M 2 AchR, there was no change neither in mRNA level nor in protein density.This study shows that adrenergic and muscarinic systems are differentially regulated following training when using results on mRNA and protein expression of these cardiac receptors.Moreover, morphological and cellular adaptations related to training seem, to some extent, to be similar as noted in hearts affected by diabetes or in heart failure.However, the modifications induced by physical training, are involved in beneficial cardiovascular modulations.

Background Improvement to maximal oxygen uptake is mainly due to myocardial adaptations brought about by physical training. As a consequence, the athlete's heart echocardiographic modifications associated with these adaptations are already well-known. We studied the relationships between maximal oxygen uptake (ml/min) and resting echocardiographic patterns in three athlete groups.Methods Tumbling (n=16), canoeing (n=12), cycling (n=12) and untrained (n=19) participants performed clinical examination and an echocardiogram. Trained groups performed a maximal graded exercise test on a cycle ergometer with gas exchange analysis.Results Sport-specific cardiac hypertrophy was observed. No significant echocardiographic difference was noted between untrained and tumbling participants. Canoeists showed higher end-diastolic thickness of the interventricular septum (P < 0.001) and left ventricle mass (P < 0.05) than untrained and higher posterior wall thickness (P < 0.001) and than untrained and tumbling participants. In comparison between untrained, tumbling and cycling participants, left ventricular end-diastolic diameter (P < 0.001) and left ventricular mass (P < 0.001) was higher in cyclists. In trained subjects studied as a global group, the main linear correlation with maximal oxygen uptake concerned left ventricular end-diastolic diameter (r=0.92; P < 0.001), left ventricular mass (r=0.60; P < 0.001) and to a lesser extent aortic (r=0.39; P < 0.01) and left atrium (r=0.36; P < 0.05) diameters and E (r=0.38; P < 0.05) and A (r=-0.33; P < 0.05) Doppler peak velocities. Each trained group showed specific correlations between echocardiographic parameters and absolute maximal oxygen uptake. No further correlation was noted with left ventricular end-diastolic diameter or left ventricle mass when each group was studied individually.Conclusions In athletes, maximal oxygen uptake is partly linked to some resting echocardiographic parameters. Specific relationships between maximal oxygen uptake and some echocardiographic parameters in relation to the sport practised are also observed.

We investigated the effects of exercise training on heart rate variability (HRV) and myocardial adrenergic and muscarinic receptors in rats. Exercise training induced a decrease in body mass while ventricular size remained unchanged, a development we considered as a relative cardiac hypertrophy. In addition, there was a reduction in the density of myocardial β1-adrenergic receptors. These structural changes were associated with functional adaptations, as illustrated by the increased response of the sinus node to sympathetic blockade.

Aims. - Myocardial adaptations to acute and chronic exercise differ with gender. Autonomic nervous system is greatly involved in these adaptations. In order to explain a part of these differences, we compared the left ventricle densities of M, muscarinic and adrenergic receptors in seven-week-old female and male rats.Methods. - Sedentary (7 females and 7 males) and trained rats (9 females and 9 males), which have performed a treadmill training protocol for eight weeks, have been studied. The left ventricular receptor densities have been quantified with the western-blot method.Results. - For all rats (male-female sedentary and male-female trained), no significant differences in M-2 muscarinic, beta(1) and beta(2) receptor densities have been observed. However, beta(3) adrenoceptor densities were significantly higher in male rats compared to female rats whatever the status, sedentary or trained (P < 0.01).Conclusion. - This data could explain partly the gender difference in myocardial adaptations to acute exercise described but not those observed after chronic exercise. (c) 2005 Elsevier SAS. Tous droits reserves.

OBJECTIVE:Physical training is known to alter several cardiovascular parameters. These adaptations are for a great part linked to an alteration of the myocardial responses to its autonomic nervous regulation. To further explain the parasympathetic and catecholamine effects, we hypothesized that endurance training could modify rat myocardial beta1, beta2, beta3 adrenoreceptors (AR) and M2 muscarinic cholinergic receptor (AchR) densities. METHODS:Two groups of adults female Wistar rats were studied: controls (C) (N = 7) and trained (T) (N = 9). An 8-wk treadmill training protocol was performed, 5 d x wk and of 1 h x d. At the end of the training session, left ventricle and atria muscle were isolated and weighed. Then, quantification of beta1, beta2, beta3 AR and M2 AchR was performed using Western blot analysis. RESULTS:M2 AchR densities were not modified in left ventricle or in atria by training (respectively, 100 +/- 22%, C vs 101 +/- 14%, T and 100 +/- 23%, C vs 119 +/- 30%, T). Concerning the left ventricle beta AR isoforms, beta1AR density was decreased in T (80 +/- 10% T vs 100 +/- 14% C, P = 0.01), beta2AR was unaltered (102 +/- 12%, T vs 100 +/- 17%, C), and beta3 AR density was increased in T (139 +/- 38% T vs 100 +/- 15% C; P < 0.05). CONCLUSIONS:Our results show for the first time that in female rats an 8-wk treadmill training protocol alters specifically the left ventricle beta AR isoforms densities but not the M2 AchR one. These results could explain some of the beneficial cardiovascular adaptations of the physically trained heart.