No abstract

We evaluated the effects of swimming and anabolic steroids (AS) on ventricular function, collagen synthesis, and the local renin-angiotensin system in rats. Male Wistar rats were randomized into control (C), steroid (S; nandrolone decanoate; 5 mg/kg sc, 2x/wk), steroid + losartan (SL; 20 mg.kg(-1).day(-1)), trained (T), trained + steroid (T+S), and trained + steroid + losartan (T+SL; n = 14/group) groups. Swimming was performed 5 times/wk for 10 wk. Serum testosterone increased in S and T+S. Resting heart rate was lower in T and T+S. Percent change in left ventricular (LV) weight-to-body weight ratio increased in S, T, and T+S. LV systolic pressure declined in S and T+S. LV contractility increased in T (P < 0.05). LV relaxation increased in T (P < 0.05). It was significantly lower in T+S compared with C. Collagen volumetric fraction (CVF) and hydroxyproline were higher in S and T+S than in C and T (P < 0.05), and the CVF and LV hypertrophy were prevented by losartan treatment. LV-ANG I-converting enzyme activity increased (28%) in the S group (33%), and type III collagen synthesis increased (56%) in T+S but not in T group. A positive correlation existed between LV-ANG I-converting enzyme activity and collagen type III expression (r(2) = 0.88; P < 0.05, for all groups). The ANG II and angiotensin type 1a receptor expression increased in the S and T+S groups but not in T group. Supraphysiological doses of AS exacerbated the cardiac hypertrophy in exercise-trained rats. Exercise training associated with AS induces maladaptive remodeling and further deterioration in cardiac performance. Exercise training associated with AS causes loss of the beneficial effects in LV function induced by exercising. These results suggest that aerobic exercise plus AS increases cardiac collagen content associated with activation of the local renin-angiotensin system.

Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced.

Our results suggest that the reduced antioxidant defense and the local NF-κB pathway play an important role in the impairment of endothelium-dependent relaxation in aorta from obese mice.

CE. Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure. Am J Physiol Heart Circ Physiol 307: H1655-H1666, 2014. First published October 10, 2014 doi:10.1152/ajpheart.00136.2014.-Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure (HF), which seems to be due to changes in cyclooxygenase (COX) pathway and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1 (TRPV1) and cannabinoid receptor type-1 (CB1). The purpose of the present study was to test the hypotheses: 1) exercise training (ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity (MSNA) in HF patients.2) The alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle.3) The alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients with ejection fractions Ͻ40% were randomized to untrained (n ϭ 17; 54 Ϯ 2 yr) or exercise-trained (n ϭ 17; 56 Ϯ 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex), MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E2 receptor-4, and thromboxane-A2 receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-B/ IB-␣ ratio. In conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression and COX-2 pathway and inflammation in skeletal muscle. heart failure; muscle sympathetic nervous system; metaboreflex; mechanoreflex; exercise training

. Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors. Am J Physiol Heart Circ Physiol 283: H2110-H2118, 2002. First published July 11, 2002 10.1152/ajpheart.00454.2002The involvement of nitric oxide (NO), prostaglandins, and calcium-dependent potassium channel (K Ca) activators on the negative modulation of phenylephrine-induced contractions was evaluated on the isolated aorta and caudal (CAU) artery obtained from rats treated with ouabain for 5 wk to induce hypertension. In ouabain-treated rats, the reactivity to phenylephrine was reduced in the endothelium-intact aorta but not the CAU segments. Endothelial modulation of phenylephrine contraction, as demonstrated by endothelium removal, NO synthase (NOS) inhibition with N -nitro-L-arginine methyl ester and aminoguanidine, as well as K Ca inhibition with tetraethylammonium, was more pronounced in segments from ouabain-treated animals, and here greater effects were seen in the aorta than in CAU. An increased expression of endothelial NOS and neuronal NOS was seen in the aorta after ouabain treatment. In CAU, only endothelial NOS was detected and ouabain treatment did not alter its expression. These results suggest that ouabain-induced hypertension is accompanied by increased NO release derived from endothelial NOS and neuronal NOS and increased release of an endothelial hyperpolarizing factor that presumably opens K Ca, all of which contribute to the increased negative modulation of the phenylephrine contraction. nitric oxide; endothelial-dependent hyperpolarizing factor; phenylephrine THE PLASMA LEVELS of an endogenous circulating Na ϩ -K ϩ -ATPase inhibitor, characterized as ouabain or a closely related compound (17,36), are increased in several animal models of hypertension (19,39), as well as in human essential hypertension (20). Several studies have shown that chronic administration of ouabain induces hypertension, an effect that seems to be linked to the inhibition of the Na ϩ -K ϩ -ATPase (10,22,23,45,54), although sodium pump inhibition seems not to be the exclusive mechanism of the ouabain-hypertensive effect (26,31,32,52). This enzyme is found in most eukaryotic cells and is the main system involved in the maintenance of sodium homeostasis and the membrane potential, essential factors for controlling vascular tone and blood pressure. It has been suggested that alterations in the activity of the sodium pump might be involved in the genesis or maintenance of hypertensive states (3, 33). Additionally, the hypertension induced by ouabain treatment has been associated with actions in the central nervous system that increase sympathetic activity by activation of the central renin-angiotensin system and impair the arterial baroreceptor reflex (22, 23) and associated with actions in the periphery that produce changes in responsiveness to contractile agents (10,26,45).In some isolated vascular preparations, acutely administered ouabain, at nanomolar concentrations, can enhance the actions of phenylephrine (43). Higher mi...

Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside–binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt–treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3–silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension.

1 Hypertension development, phenylephrine-induced contraction and Na + ,K + -ATPase functional activity and protein expression in aorta (AO), tail (TA) and superior mesenteric (SMA) arteries from ouabain-(25 mg day 71, s.c., 5 weeks) and vehicle-treated rats were evaluated. 2 Ouabain treatment increased systolic blood pressure (127+1 vs 160+2 mmHg, n=24, 35; P50.001) while the maximum response to phenylephrine was reduced (P50.01) in AO (102.8+3.9 vs 67.1+10.1% of KCl response, n=12, 9) and SMA (82.5+7.5 vs 52.2+5.8%, n=12, 9). 3 Endothelium removal potentiated the phenylephrine response to a greater extent in segments from ouabain-treated rats. Thus, dierences of area under the concentration-response curves (dAUC) in endothelium-denuded and intact segments for control and ouabain-treated rats were, respectively: AO, 56.6+9.6 vs 198.3+18.3 (n=9, 7); SMA, 85.5+15.4 vs 165.4+24.8 (n=6, 6); TA, 13.0+6.1 vs 39.5+10.4% of the corresponding control AUC (n=6, 6); P50.05. 4 The relaxation to KCl (1 ± 10 mM) was similar in segments from both groups. Compared to controls, the inhibition of 0.1 mM ouabain on KCl relaxation was greater in AO (dAUC: 64.8+4.6 vs 84.0+5.1%, n=11, 14; P50.05), similar in SMA (dAUC: 39.1+3.9 vs 43.3+7.8%, n=6, 7; P40.05) and smaller in TA (dAUC: 62.1+5.5 vs 41.4+8.2%, n=12, 13; P50.05) in ouabaintreated rats. 5 Protein expression of both a 1 and a 2 isoforms of Na + ,K + -ATPase was augmented in AO, unmodi®ed in SMA and reduced in TA from ouabain-treated rats. 6 These results suggest that chronic administration of ouabain induces hypertension and regional vascular alterations, the latter possibly as a consequence of the hypertension.