Estrogens [E(2)] exert direct and indirect effects that can modulate the development of cardiac disease. However, the precise mechanisms that are involved remain undefined. Our objective was to investigate whether E(2) affected the activity and expression of constitutive nitric oxide synthase (NOS) isoforms (NOS3 and NOS1) in cardiac hypertrophy induced by thoracic aortic constriction (TAC). Ovariectomized (Ovx) and nonovariectomized Wistar rats were subjected to TAC. Ovx animals received E(2) or placebo 3 wk after surgery for 11 wk. Afterward cardiac function and degree of left ventricular hypertrophy were assessed by echocardiography. NOS activity and expression were studied by biochemical techniques. TAC led to significant left ventricular hypertrophy (>90%) irrespective of hormonal status. Cardiac performance declined more in TAC+Ovx (-20%, P < 0.015) than in the two other TAC groups [TAC and TAC+Ovx+E(2)]. Total NOS activity decreased significantly in the Ovx groups. In response to TAC, total NOS activity increased whatever the E(2) status. Specific NOS3 activity dramatically decreased in the Ovx groups (-55%, P < 0.009) and was unaltered by TAC. By using coimmunoprecipitation assays, we showed that NOS3/caveolin-1 complexes negatively regulated NOS3 activity as a function of E(2) status. On the other hand, NOS1 expression and activity were markedly increased in hypertrophied myocardium (P < 0.003), irrespective of E(2) status. This study demonstrates a differential regulation of NOS expression and activity in response to pressure overload and E(2) status, the former being mainly involved in the induction of NOS1, whereas the latter regulated NOS3 activity and in turn cardiac function.

The aim of the study was to find out whether administration of selenium (Se) will protect the immature heart against ischemia/reperfusion.The control pregnant rats were fed laboratory diet (0.237 mg Se/kg diet); experimental rats received 2 ppm Na(2)SeO(3) in the drinking water from the first day of pregnancy until day 10 post partum. The concentration of Se in the serum and heart tissue was determined by activation analysis, the serum concentration of NO by chemiluminescence, cardiac concentration of lipofuscin-like pigment by fluorescence analysis. The 10 day-old hearts were perfused (Langendorff); recovery of developed force (DF) was measured after 40 min of global ischemia. In acute experiments, 10 day-old hearts were perfused with selenium (75 nmol/l) before or after global ischemia. Sensitivity to isoproterenol (ISO, pD(50)) was assessed as a response of DF to increasing cumulative dose.Se supplementation elevated serum concentration of Se by 16%. Se increased ischemic tolerance (recovery of DF, 32.28 +/- 2.37 vs. 41.82 +/- 2.91%, P < 0.05). Similar results were obtained after acute administration of Se during post-ischemic reperfusion (32.28 +/- 2.37 vs. 49.73 +/- 4.40%, P < 0.01). The pre-ischemic treatment, however, attenuated the recovery (23.08 +/- 3.04 vs. 32.28 +/- 2.37%, P < 0.05). Moreover, Se supplementation increased the sensitivity to the inotropic effect of ISO, decreased cardiac concentration of lipofuscin-like pigment and serum concentration of NO. Our results suggest that Se protects the immature heart against ischemia/reperfusion injury. It seems therefore, that ROS may affect the function of the neonatal heart, similarly as in adults.

Rakusan K, Chvojkova Z, Oliviero P, Ostadalova I, Kolar F, Chassagne C, Samuel JL, Ostadal B. ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats. Am J Physiol Heart Circ Physiol 292: H1237-H1244, 2007. First published December 1, 2006; doi:10.1152/ajpheart.00965.2006.-Chronic hypoxia has been shown to stimulate myocardial microvascular growth and improve cardiac ischemic tolerance in young and adult rats. The aim of this study was to determine whether the ANG II type 1 receptor (AT1) pathway was involved in these processes. Newborn Wistar rats, exposed to chronic intermittent hypoxia (8 h/day) for 10 days, were simultaneously treated with AT1 receptor blocker irbesartan and compared with untreated animals. The major finding is that chronic hypoxia increased the capillary supply of myocardial tissue, which was even more pronounced in hypertrophied right ventricle, whereas increased arteriolar supply was found only in the left ventricle. This angiogenic response was completely prevented by irbesartan. Moreover, chronic hypoxia improved the postischemic recovery of cardiac contractile function during reperfusion, and this protective effect was also completely abolished by irbesartan. Chronic hypoxia increased the myocardial density of AT1 but not of ANG II type 2 receptor subtypes, whereas the effect of irbesartan was not significant. The expression of caveolin-1␣ markedly increased in response to chronic hypoxia, and irbesartan prevented this effect. Neither hypoxia nor irbesartan treatment altered the expression of nitric oxide synthase 3, heat shock protein 90, and VEGF. It is concluded that the AT1 receptor pathway plays an important role in coronary angiogenesis and improved cardiac ischemic tolerance induced in neonatal rats by chronic hypoxia.angiotensin II receptors; ischemia-reperfusion; caveolin-1 ADAPTATION TO CHRONIC HYPOXIA increases cardiac tolerance to all major deleterious consequences of acute oxygen deprivation in both adult and immature heart. In addition to the protective effect, chronic hypoxia may also induce other adaptive responses, including hypoxic pulmonary hypertension and right ventricular (RV) hypertrophy (22). This is a beneficial adaptation, allowing the RV to cope with an increased afterload and to maintain cardiac output. Although many potential factors have been proposed to play a role in the mechanisms of cardiac adaptation to chronic hypoxia, the available data are not sufficiently conclusive. Moreover, a substantial amount of information concerning the adaptive response was obtained from the adult myocardium, whereas much less is known about this process in the immature heart. However, clinical relevance of the developmental approach is obvious: chronic hypoxia is the main pathophysiological feature of hypoxemic congenital heart disease. Understanding the mechanisms by which these malformations modify the myocardium and how they impact on the adaptive mechanisms during ischemia may provide ins...

We investigated the effect of ESR gene-based selection on an improvement of litter size in the herds in real (nonexperimental) conditions. The pigs were selected for three years. In the tested population the pigs were mated according to a breeding scheme where the individuals with at least one ESR-B allele were preferred in the selection. In the control group (CP; n = 140) the pigs were mated just according to a breeding scheme without knowledge of the ESR genotype. We observed a significant increase in litter size (total number of born, number of born alive and number of weaned piglets per litter) in the final tested ESR-selected population (LP; n = 184) and an insignificant increase in CP as compared with the original population (OP; n = 155). After the selection we could observe a significant increase in the frequency of allele B in LP. Frequency of the genotypes AB and BB increased in both LP and CP; the distribution of the genotypes changed significantly only in LP. An association analysis of the ESR gene effects on reproductive traits in LP showed no significant differences between the genotypes. The results of our study suggest that ESR gene-based selection can be successful also in small herds, under real (non-experimental) conditions with a respect for general breeding principles and limitations and during a short period. An examination of a larger sample population as well as an analysis of selection consequences on other traits (meat and carcass quality) could bring a more conclusive evaluation of ESR-based selection. Nevertheless, the results are encouraging especially for small breeding farms taking a perspective of better litter size improvement.