Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta.

Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose-dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5-fold higher) than that needed to obtain 29 nmol/L of HgCl2 on the vascular function. Three-month-old male Wistar rats received intramuscular (i.m.) HgCl2 for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l-NAME (100 µmol/L). The phosphorylated-eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE-induced contractions, while l-NAME had no effects and indomethacin (10 µmol/L), losartan (10 µmol/L) and apocynin (30 µmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase-2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin-angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.

Chronic mercury exposure impairs the sympathovagal control of the rat heart.

Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl2 (1st dose 4.6 µg/kg followed by 0.07 µg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk.

Altered cardiovascular reactivity to mental stress in patients with multiple sclerosis.

Cold pressure test (CPT) and mental stress test (MST) are distinct tests usually leading to blood pressure (BP) and heart rate (HR) increase. Their patterns in multiple sclerosis (MS) are still unknown. This study assessed cardiovascular reactivity to MST and CPT in patients with MS and controls. MST was performed with Stroop test card. CPT was performed with cold stimulus. The BP and HR were digitally recorded at rest and test phases. The delta (Δ) and the variance of BP and HR were compared between patients and controls. Patients with MS had lower Δ of diastolic BP and HR induced by MST than controls. There were no differences between patients and controls with CPT. The reduced autonomic reactivity to MST but not with CPT suggests that specific central nervous system pathways involved in MST may be responsible for autonomic findings in MS.

Chronic Mercury Exposure in Prehypertensive SHRs Accelerates Hypertension Development and Activates Vasoprotective Mechanisms by Increasing NO and H2O2 Production.

Mercury is a heavy metal associated with cardiovascular diseases. Studies have reported increased vascular reactivity without changes in systolic blood pressure (SBP) after chronic mercury chloride (HgCl2) exposure, an inorganic form of the metal, in normotensive rats. However, we do not know whether individuals in the prehypertensive phase, such as young spontaneously hypertensive rats (SHRs), are susceptible to increased arterial blood pressure. We investigated whether chronic HgCl2 exposure in young SHRs accelerates hypertension development by studying the vascular function of mesenteric resistance arteries (MRAs) and SBP in young SHRs during the prehypertensive phase. Four-week-old male SHRs were divided into two groups: the SHR control group (vehicle) and the SHR HgCl2 group (4 weeks of exposure). The results showed that HgCl2 treatment accelerated the development of hypertension; reduced vascular reactivity to phenylephrine in MRAs; increased nitric oxide (NO) generation; promoted vascular dysfunction by increasing the production of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2); increased Gp91Phox protein levels and in situ levels of superoxide anion (O2·-); and reduced vasoconstrictor prostanoid production compared to vehicle treatment. Although HgCl2 accelerated the development of hypertension, the HgCl2-exposed animals also exhibited a vasoprotective mechanism to counterbalance the rapid increase in SBP by decreasing vascular reactivity through H2O2 and NO overproduction. Our results suggest that HgCl2 exposure potentiates this vasoprotective mechanism against the early establishment of hypertension. Therefore, we are concluding that chronic exposure to HgCl2 in prehypertensive animals could enhance the risk for cardiovascular diseases.

Chronic Cadmium Exposure Accelerates the Development of Atherosclerosis and Induces Vascular Dysfunction in the Aorta of ApoE-/- Mice.

Cadmium exposure is related to cardiovascular diseases, including hypertension, atherosclerosis, increased oxidative stress, endothelial dysfunction, and specific biochemical changes induced by this metal. Thus, we aimed to investigate whether cadmium exposure induces endothelial dysfunction, accelerates atherosclerotic plaque formation in the aorta, and enhances oxidative stress in apolipoprotein E knockout (ApoE-/-) mice. Experiments were performed in 14-week-old male wild-type and ApoE-/- mice. ApoE-/- mice received cadmium (CdCl2 100 mg/L in drinking water for 28 days) or vehicle (distilled water). After treatment, vascular reactivity to phenylephrine, acetylcholine, and sodium nitroprusside was analyzed using isolated aorta. Bone marrow cells were isolated to assess the production of nitric oxide and reactive oxygen and nitrogen species. ApoE-/- cadmium-treated mice had higher cholesterol levels than non-exposed mice. Cadmium exposure decreased the vasodilatation response to acetylcholine in aortic ring of ApoE-/- mice, though no changes in phenylephrine or sodium nitroprusside responses were observed. L-NAME reduced vasodilator responses to acetylcholine; this effect was lower in ApoE-/- cadmium-treated mice, suggesting reduction in nitric oxide (NO) bioavailability. Moreover, in bone marrow cells, cadmium decreased cytoplasmic levels of NO and increased superoxide anions, hydrogen peroxide, and peroxynitrite in ApoE-/- mice. Morphological analysis showed that cadmium exposure increased plaque deposition in the aorta by approximately 3-fold. Our results suggest that cadmium exposure induces endothelial dysfunction in ApoE-/- mice. Moreover, cadmium increased total cholesterol levels, which may promote the early development of atherosclerosis in the aorta of ApoE-/- mice. Our findings support the hypothesis that cadmium exposure might increase the risk of atherosclerosis.

Post-resistance exercise hypotension in spontaneously hypertensive rats is mediated by nitric oxide.

1. Postexercise hypotension (PEH) plays an important role in the non-pharmacological treatment of hypertension. It is characterized by a decrease in blood pressure (BP) after a single bout of exercise in relation to pre-exercise levels. 2. The present study investigated the effect of a single session of resistance exercise, as well as the effect of nitric oxide (NO) and the autonomic nervous system (ANS), in PEH in spontaneously hypertensive rats (SHR). 3. Catheters were inserted into the left carotid artery and left jugular vein of male SHR (n = 37) for the purpose of measuring BP or heart rate (HR) and drug or vehicle administration, respectively. Haemodynamic measurements were made before and after acute resistance exercise. The roles of NO and the ANS were investigated by using N(G)-nitro-L-arginine methyl ester (L-NAME; 15 mg/kg, i.v.) and hexamethonium (20 mg/kg, i.v.) after a session of acute resistance exercise. 4. Acute resistance exercise promoted a pronounced reduction in systolic and diastolic BP (-37 +/- 1 and -8 +/- 1 mmHg, respectively; P < 0.05), which was suppressed after treatment with L-NAME. The reduction in systolic BP caused by exercise (-37 +/- 1 mmHg) was not altered by the administration of hexamethonium (-38 +/- 2 mmHg; P > 0.05). After exercise, the decrease in diastolic BP was greater with hexamethonium (-26 +/- 1 mmHg; P < 0.05) compared with the decrease caused by exercise alone. 5. The results suggest that acute resistance exercise has an important hypotensive effect on SHR and that NO plays a crucial role in this response.

Testosterone deficiency prevents left ventricular contractility dysfunction after myocardial infarction.

Testosterone may affect myocardial contractility since its deficiency decreases the contraction and relaxation of the heart. Meanwhile, testosterone replacement therapy has raised concerns because it may worsen cardiac dysfunction and remodeling after myocardial infarction (MI). In this study, we evaluate cardiac contractility 60 days after MI in rats with suppressed testosterone. Male Wistar rats underwent bilateral orchidectomy one week before the ligation of the anterior descending left coronary artery. The animals were divided into orchidectomized (OCT); MI; orchidectomized + MI (OCT + MI); orchidectomized + MI + testosterone (OCT + MI + T) and control (Sham) groups. Eight weeks after MI, papillary muscle contractility was analyzed under increasing calcium (0.62, 1.25, 2.5 and 3.75 mM) and isoproterenol (10-8 to 10-2 M) concentrations. Ventricular myocytes were isolated for intracellular calcium measurements and assessment of Ca2+ handling proteins. Contractility was preserved in the orchidectomized animals after myocardial infarction and was reduced when testosterone was replaced (Ca2+ 3.75 mM: Sham: 608 ± 70 (n = 11); OCT: 590 ± 37 (n = 16); MI: 311 ± 33* (n = 9); OCT + MI: 594 ± 76 (n = 7); OCT + MI + T: 433 ± 38* (n=4), g/g *p < 0.05 vs Sham). Orchidectomy also increased the Ca2+ transient amplitude of the ventricular myocytes and SERCA-2a protein expression levels. PLB phosphorylation levels at Thr17 were not different in the orchidectomized animals compared to the Sham animals but were reduced after testosterone replacement. CAMKII phosphorylation and protein nitrosylation increased in the orchidectomized animals. Our results support the view that testosterone deficiency prevents MI contractility dysfunction by altering the key proteins involved in Ca2+ handling.

Low-salt diet increases NO bioavailability and COX-2 vasoconstrictor prostanoid production in spontaneously hypertensive rats.

AIMS: The ability of dietary sodium restriction to reduce the incidence of cardiovascular mortality and improve vascular function in hypertension still remains poorly understood. The aim of this study was to observe the effects of a long period of salt restriction on the vascular reactivity of mesenteric resistance arteries of SHRs. METHODS: Male SHRs received either standard-salt diet (0.3% NaCl) or low-salt diet (0.03% NaCl) for 28weeks. Vascular reactivity was studied in mesenteric artery segments and the influence of cyclooxygenase-2 (COX-2), reactive oxygen species (ROS) and participation of the renin-angiotensin system were analyzed. KEY FINDINGS: Decreased salt intake did not affect phenylephrine-induced vasoconstriction but increased acetylcholine-induced vasodilatation and also increased the response to phenylephrine after inhibition of NO synthase by L-NAME (100µM) and iNOS protein expression was elevated. Cyclooxygenase inhibitor indomethacin (10µM) and COX-2 inhibitor NS 398 (1µM) decreased the reactivity to phenylephrine in low-salt-treated group, and COX-2 protein expression was elevated in low-salt group. The effects of apocynin (10µM); superoxide anion scavenger, tiron (1mM); hydrogen peroxide scavenger, catalase (1000UmL(-1)); and ACE and AT1 receptor blockers, enalapril (10µM) and losartan (10µM) on vascular reactivity were not different between two groups. The levels of AT1 protein expression were similar in both groups. SIGNIFICANCE: Low-salt diet modulates mesenteric vascular responses via increased NO bioavailability suggested by increased iNOS protein expression and vasoconstrictor prostanoid production via COX-2 pathway, in SHRs. Neither ROS nor the local renin-angiotensin system is involved in these responses.

Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension.

BACKGROUND AND PURPOSE: Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension. EXPERIMENTAL APPROACH: Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg · kg(-1) · day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg · kg(-1) · day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg · kg(-1) · day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used. KEY RESULTS: Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-α expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment. CONCLUSIONS AND IMPLICATIONS: COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage.

Eucalyptol, an essential oil, reduces contractile activity in rat cardiac muscle.

Eucalyptol is an essential oil that relaxes bronchial and vascular smooth muscle although its direct actions on isolated myocardium have not been reported. We investigated a putative negative inotropic effect of the oil on left ventricular papillary muscles from male Wistar rats weighing 250 to 300 g, as well as its effects on isometric force, rate of force development, time parameters, post-rest potentiation, positive inotropic interventions produced by Ca2+ and isoproterenol, and on tetanic tension. The effects of 0.3 mM eucalyptol on myosin ATPase activity were also investigated. Eucalyptol (0.003 to 0.3 mM) reduced isometric tension, the rate of force development and time parameters. The oil reduced the force developed by steady-state contractions (50% at 0.3 mM) but did not alter sarcoplasmic reticulum function or post-rest contractions and produced a progressive increase in relative potentiation. Increased extracellular Ca2+ concentration (0.62 to 5 mM) and isoproterenol (20 nM) administration counteracted the negative inotropic effects of the oil. The activity of the contractile machinery evaluated by tetanic force development was reduced by 30 to 50% but myosin ATPase activity was not affected by eucalyptol (0.3 mM), supporting the idea of a reduction of sarcolemmal Ca2+ influx. The present results suggest that eucalyptol depresses force development, probably acting as a calcium channel blocker.

Left ventricular length dependent activation in the isovolumetric rat heart.

STUDY OBJECTIVE: The aim of the study was to examine, in a whole heart preparation, the relationship between length changes in cardiac muscle and tension development and length dependent activation. DESIGN: Rat hearts were perfused by the Langendorff technique and isovolumetric pressure changes in the left ventricle, produced by increasing diastolic pressures (0, 5, 10, 15, 20, 25 mm Hg), were studied at different calcium concentrations (0.5, 1.25, 2.5, 3.75 mmol.litre-1). EXPERIMENTAL MATERIALS: 20 whole heart preparations were obtained from albino rats of either sex, weight 180-240 g (females) and 220-330 g (males). MEASUREMENTS AND MAIN RESULTS: In a comparison of ventricular diastolic upsilon systolic pressure curves, normalised with respect to maximum isovolumetric systolic pressure, there was a separation and an upward displacement of the curves with increments in calcium concentration in the perfusate. CONCLUSIONS: The results show, as in isolated preparations, that there is length dependent activation in the whole rat heart.

Changes in performance of the surviving myocardium after left ventricular infarction in rats.

STUDY OBJECTIVE: The aim was to investigate left ventricular performance of infarcted hearts during scar formation and development of hypertrophy in the surviving myocardium. DESIGN: Hearts were perfused according to the Langendorff technique and left ventricular function curves were obtained by inserting a distensible balloon into the ventricular cavity. The isovolumetric systolic pressure was measured as diastolic pressure was changed from 0 to 25 mm Hg and during inotropic interventions produced by Ca and isoprenaline. EXPERIMENTAL MATERIALS: Hearts were obtained from albino rats of either sex, 180-250 g, killed 1, 3, 7 or 14 d after left coronary artery ligation (n = 24) or sham operation (n = 26). Normal rats (n = 6) were used as additional controls. MEASUREMENTS AND MAIN RESULTS: After infarction, there was a progressive and almost parallel displacement of the ventricular function curves toward higher diastolic pressures. The positive chronotropic response to isoprenaline was similar in infarcted and non-infarcted hearts. The inotropic response to Ca and isoprenaline, however, was significantly depressed in the infarcted hearts throughout the observation period. CONCLUSIONS: Hypertrophy in the surviving myocardium did not result in improvement of the left ventricular systolic function assessed under in vitro conditions during the first two weeks after infarction. The decreased inotropic response of the infarcted left ventricle to isoprenaline is likely to be dependent on the reduced Ca sensitivity of the surviving myocardium.

A single resistance exercise session improves myocardial contractility in spontaneously hypertensive rats.

Resistance training evokes myocardial adaptation; however, the effects of a single resistance exercise session on cardiac performance are poorly understood or investigated. This study aimed to investigate the effects of a single resistance exercise session on the myocardial contractility of spontaneously hypertensive rats (SHRs). Male 3-month-old SHRs were divided into two groups: control (Ct) and exercise (Ex). Control animals were submitted to sham exercise. Blood pressure was measured in conscious rats before the exercise session to confirm the presence of arterial hypertension. Ten minutes after the exercise session, the animals were anesthetized and killed, and the hearts were removed. Cardiac contractility was evaluated in the whole heart by the Langendorff technique and by isometric contractions of isolated left ventricular papillary muscles. SERCA2a, phospholamban (PLB), and phosphorylated PLB expression were investigated by Western blot. Exercise increased force development of isolated papillary muscles (Ex=1.0±0.1 g/mg vs Ct=0.63±0.2 g/mg, P<0.05). Post-rest contraction was greater in the exercised animals (Ex=4.1±0.4% vs Ct=1.7±0.2%, P<0.05). Papillary muscles of exercised animals developed greater force under increasing isoproterenol concentrations (P<0.05). In the isolated heart, exercise increased left ventricular isovolumetric systolic pressure (LVISP; Δ +39 mmHg; P<0.05) from baseline conditions. Hearts from the exercised rats presented a greater response to increasing diastolic pressure. Positive inotropic intervention to calcium and isoproterenol resulted in greater LVISP in exercised animals (P<0.05). The results demonstrated that a single resistance exercise session improved myocardial contractility in SHRs.

Effects of ouabain on the pressor response to phenylephrine and on the sodium pump activity in diabetic rats.

The diabetes mellitus insulin-dependent is usually associated with cardiovascular disorders and with changes in the activity of the Na(+),K(+)-ATPase. The effects of ouabain, a Na(+),K(+)-ATPase inhibitor, on the pressor response of 7-day streptozotocin-induced diabetes were investigated in anesthetized rats and on the vascular reactivity of the perfused rat tail vascular bed. Diabetes was characterized by hyperglycemia (86+/-7.8 vs. 471+/-18.5 mg/dl) without changes in arterial blood pressure. Blood pressure increased after the treatment with 18 microg/kg ouabain in controls but not in diabetic rats; acute hyperglycemia, in non-treated rats, did not change these effects. Control tail vascular beds showed increased maximal response to phenylephrine after treatment with 10 nM ouabain for 1 h; this response was abolished in streptozotocin-treated rats. These rats showed an increased sensitivity to phenylephrine without changing the maximal vasoconstrictor response when compared to control rats. The relaxation induced by acetylcholine was reduced in diabetic rats. The functional activity of the Na(+),K(+)-ATPase was inhibited in vascular beds from diabetic rats, when compared to control rats, and the inhibition of the Na(+),K(+)-ATPase with 10 nM ouabain was not effective in these rats. Results suggested that in 7-day diabetic rats, the increase of arterial blood pressure or the sensitization of the vascular bed produced by ouabain is lost as a consequence of the reduction of the functional activity of the Na(+), K(+)-ATPase probably as a result of insulin lack and a deficient endothelial nitric oxide activity.

Changes in collagen content in the residual myocardium surviving after infarction in rats. Influence of propranolol or hydralazine therapy.

The changes occurring in the collagen content in the residual myocardium after infarction have been poorly studied. The aim of this study was to determine the changes in the collagen content in the right and left ventricular muscle of chronically infarcted hearts. Male albino rats were submitted to ligature of the left coronary artery to produce infarction (Inf). Controls underwent a sham surgery (Sh). Inf rats were divided into groups designed to receive chronic therapy with propranolol (Prop, 1 g/l, n = 10) or hydralazine (Hydr, 0.125 g/l, n = 10) dissolved in the drinking water. One group of Inf rats (n = 12) and the Sh group (n = 10) received no treatment. The animals were killed 1 month after surgery to obtain the cardiac wet weights and to determine protein and hydroxyproline (OH-Pro) concentrations in the right ventricle (RV) free wall and in the left ventricular remaining muscle (LV), including the interventricular septum. Inf determined a 42% increase of the RV weight to body weight ratio (Sh = 0.57 +/- 0.04 mg/g; Inf = 0.81 +/- 0.06 mg/g; p < 0.05) and a 64% increase of OH-Pro concentration (Sh = 450 +/- 25 micrograms/g; Inf = 738 +/- 32 micrograms/g; p < 0.05). In Inf hearts the LV OH-Pro concentration increased similarly as in the RV. No effect of drug therapy was observed in the LV. In the RV however, propranolol reduced the hypertrophy and the OH-Pro concentration by the same amount (around 30%). Hydr on the other hand reduced OH-Pro and tended to increase hypertrophy. We conclude that a similar collagen deposition occurs in the myocardium of both ventricles after infarction in rats. Prop and Hydr were able to partially reduce this collagen increase in the right but not in the left ventricle.

Characteristics of myocardial contractions activated under depolarizing conditions.

Guinea pig papillary muscles were used to study the activation of myocardial contractions under depolarizing conditions. Depolarization promoted by TKBa (normal Tyrode solution containing KCl and BaCl2) and TKAdr (normal Tyrode solution containing KCl and adrenaline) inactivates the fast Na current and under these conditions only slow responses are available to activate contractions. Since the slow response is sensitive to changes in rate and rhythm, we searched for mechanical correlates using isometrically contracting preparations to study the force-frequency relationship as well as rest potentiation. We also investigated if contractions are dependent only on the slow response or if the complete action potential plays a special role in the activation of contractions. We conclude that the slow response is the main mechanism for the activation of myocardial contraction, because complete mechanical activation was observed under depolarizing conditions. However, the electrical behavior of the slow response is reflected in the mechanical behavior of the depolarized preparations. At high rates, disturbances of excitation occur in depolarized cells and contractions appear to be bigeminal or with 2:1 block. Furthermore, after long pauses, post-rest contractions are depressed and increase progressively with repetitive stimulation, probably due to changes in the latency and threshold of the slow response. The complete action potential also plays a role in the activation of myocardial contractions which is necessary for the resting potentiation phenomena and also to avoid the larger depression of the rest contractions that can be seen in depolarized muscles when the pause is prolonged. This behavior seems to be related to the decrease of intracellular Na concentration produced by the inhibition of the fast inward Na-current.

Effects of mercury on the contractility of isolated rat cardiac muscle.

The effects of increasing concentrations of mercury (Hg2+) chloride (1, 2.5, 5 and 10 microM) were studied on isometrically contracting papillary muscles from female rats (Wistar, EPM strain) weighing 150 to 180 g. Hg2+ promoted an increase of 12.7 +/- 2.2% in the developed force at 1 microM. At 2.5 microM, force values were similar to control, decreasing progressively as Hg2+ concentration increased to 5 (-13 +/- 6.4%) and 10 microM (-37 +/- 12.3%). Potentiated post-rest contractions (PRC) were also determined after 15-, 30- and 60-s pauses. There was a progressive reduction of the potentiated PRCs relative to their respective steady-state control contractions with increasing concentrations of HgCl2. Since in several tissues including myocardium Hg2+ inhibits the activity of Ca2+ and Na(+)-K(+)-ATPases the results described here suggest that Hg2+, at lower concentrations, could increase force by inhibiting Na(+)-K(+)-ATPase, while at higher concentrations Hg2+ would decrease relative PRC potentiation by inhibiting sarcoplasmic reticulum Ca(2+)-ATPase.

Length-dependent inotropic changes in cardiac muscle.

1. Length-dependent changes of the inotropic state of rabbit atrial strips were studied using inotropic interventions. Increases in extracellular calcium and adrenaline were used as positive inotropic agents, whereas acetylcholine and verapamil were the negative inotropic agents. Length-tension curves were normalized with respect to maximal developed tension and length. 2. The expected length-tension relations were obtained when plotted in a conventional manner. However, when length-tension curves were normalized with respect to maximal developed tension and length, a length-dependent activation was indicated by the separation of the curves. 3. These results suggest that length-dependent activation altered the inotropic state of cardiac muscle when length changed.

Time-dependent changes of left ventricular contractility in Langendorff perfused hearts from renovascular hypertensive rats.

1. The contractile activity of the hypertrophied myocardium was investigated in Langendorff perfused hearts from one-kidney one-clip (1K1C) renovascular hypertensive rats. 2. Hearts obtained from control and renovascular hypertensive animals were studied 15, 30 and 60 days after sham operation (SO) or renovascular hypertension induction. Rats were anesthetized with ether and mean blood pressure (MBP) and heart rate (HR) were measured. The hearts were then excised and perfused with Krebs solution and bicarbonate buffer, at 31 degrees C, with a perfusion pressure of 75 mmHg, beating spontaneously. The left ventricular function curves were evaluated by measuring the isovolumic systolic pressure (ISP) obtained at diastolic pressures (DP) of 0, 10, 20 and 30 mmHg in 0.62, 1.25 and 2.5 mM extracellular calcium. After the experiments the left ventricle (LV) was dissected, blotted and dried to obtain the dry and wet weights. 3. The 1K1C animals were hypertensive and displayed LV hypertrophy. The LV function curves showed the expected behavior, being similar for all 3 calcium concentrations used for the 15-day groups. However, at 30 days, ISPs were lower than those from the SO control group. Moreover, after 60 days ISPs from 1K1C rat ventricles were higher than controls in 0.62 mM calcium for all DPs. For all other DPs, ISP from 1K1C and control ventricles were similar. Normalization of ISP to LV dry weight showed that the hypertrophied ventricles, at any time and at all calcium concentrations used, developed less pressure by ventricular mass than SO controls. 4. Absolute ISP results suggest changes in the contractile machinery characteristics, not only as a function of the pressure overload but also as a function of the hypertension time course, and that ISP normalization to ventricular mass demonstrated the lower capacity of the hypertrophied muscle to generate force and pressure.

Post-rest contractions of amphibian cardiac muscle.

Post-rest potentiated contractions have been reported to be more dependent on Ca2+ stored in intracellular sites than on transmembrane Ca2+ influx. The phenomenon was examined using toad ventricular strips contracting isometrically and superfused with Ringer solution. Toad ventricular strips did not present post-rest potentiation, a fact that may be explained by the reduced volume of the sarcoplasmic reticulum in the amphibian myocardium. Potentiated post-rest contractions were obtained after calcium influx blockade with 10 microM verapamil or 2 mM Mn2+ and the slow reduction of extracellular Ca2+ concentration obtained by slowly exchanging the bath fluid was accompanied by a progressive decrease of both steady-state and post-rest contractions. These data confirm the observations made on other species regarding the post-rest potentiation phenomenon and support the suggestion of the dependence of post-rest potentiation on activator calcium liberated from intracellular stores.