Biomedical subjects
Publications and source records attributed to D V Vassallo.
Contractility changes and adaptive responses resulting from acute left ventricular (LV) myocardial infarction are not restricted to the LV myocardium. The reduced LV function increased the right ventricular (RV) pressure load and neurohumoral factors, activated by the infarction
Skinned fiber preparations are used to obtain the maximal contractile activation of isolated myocardial preparations. Tetanic contractions elicited in the presence of sarcoplasmic reticulum inhibitors have also been used as an alternative method to produce maximal active tension in the intact myocardium. In this work our purpose was to define the best conditions to obtain tetanic contractions in the rat myocardium and to compare the influence of muscle length and inotropic interventions (Ca2+ and Bay K 8644) in the tension produced in twitches and tetanic contractures. Papillary muscles were mounted in a perfusion chamber to record isometric force. Tetanic contractions were elicited by using suprathreshold stimulation with rectangular pulses (10 ms duration) at 5 Hz in the presence of 2.5 mM caffeine. Caffeine depressed the twitch tension but the tetanic tension was similar to that produced under steady-state stimulation (0.5 Hz) in control conditions. Tetanic and twitch tensions were similar along the whole extension of the length-tension curve and under the positive inotropic effects produced by Ca2+ (0.25 to 3.75 mM) or by the Ca(2+)-channel agonist Bay K 8644 (1 microM). During long tetanic stimuli (60 s) a time-dependent tension decay was observed. This decay was prolonged by reducing the extracellular K+ from 5.4 to 1.0 microM, suggesting that Ca2+ extrusion through the Na-Ca exchanger seems to occur during tetanic stimulation. Since tetanic tension was never higher than the tension obtained in twitches elicited at the same Ca2+ concentration (0.5 Hz), we conclude that tetanic contractures represent a useful tool to investigate the contractile response of intact myocardial preparations with a nonfunctional sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)
Ouabain, a cardiac glycoside, binds to the alpha-subunits of Na+, K(+)-ATPase and inhibits Na+ pump activity. It has been proposed that endogenous ouabain, by inhibiting vascular Na+, K(+)-ATPase, can increase vascular resistance and thus may contribute to hypertension. One of the consequences of inhibition of the membrane Na+ pump is enhanced responsiveness of vascular smooth muscle to vasopressor substances. The purpose of the present study was to determine whether ouabain can enhance the responsiveness of the vasculature in hypertension. In the present study 100 microM ouabain enhanced the contractile response elicited by phenylephrine in isolated, perfused tail arteries from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. The enhanced contractile response was more pronounced in the arteries of the SHR. We demonstrated that this concentration of ouabain inhibits the Na+ pump activity, measured as ouabain-sensitive 86Rb uptake, by about 65%, in isolated tail arteries. We conclude that ouabain can sensitize the vascular smooth muscle to the effects of vasopressor substances and this effect is more pronounced in genetically hypertensive rats. Endogenous ouabain may contribute to the pathophysiology of hypertension by enhancing vascular tone.
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.
Changes of contractility resulting from changes in stimulation pattern (post-extrasystolic potentiation - PESP) were investigated in right ventricular papillary muscles from female albino rats (EPM strain, 160-200 g). The preparations were superfused with bicarbonate buffered solution at 24 +/- 0.5 degrees C, and stimulated at 0.5 Hz. Maintained paired stimulation was performed at several coupling intervals (360, 500, 660, 770 and 920 ms) with normal Krebs for 30 s. After treatment with ryanodine (1 microM), used as an inhibitor of the release of sarcoplasmic reticulum Ca2+ activity, the same protocol was repeated in the presence of normal Krebs, low Na+ (80 mM, LiCl used as substitute) and low K+ concentrations to change the level of activity of the Na+/Ca2+ exchange mechanism. With normal Krebs, paired pulse stimulation produced a maintained potentiation of the post-extrasystolic beat and an extrasystole with a reduced force generation when compared to the control steady-state contraction. As the interval between the extrasystole and the normal beat was increased the potentiation of the post-extrasystolic beat was reduced and the force of the extrasystole was increased. Ryanodine treatment reduced the force of contraction and increased its duration, and the pattern of the PESP phenomenon was altered. Both the post-extrasystolic and the extrasystolic beats were potentiated compared to the steady-state contraction obtained under ryanodine treatment. The extrasystole displayed a greater potentiation than the post-extrasystolic beat. As the interval between them increased the amplitude of the extrasystolic beat was enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
The toxic effects of HgCl2 (1, 2.5, 5, and 10 microM) were studied in isolated, isometrically contracting rat papillary muscles and frog ventricular strips. In rat papillary muscles 1 microM Hg2+ produced a small increase in the force of contraction. Higher concentrations of HgCl2 produced a dose-dependent decrease in contractile force. The rate of force development was affected differently, increasing at 1 and 2.5 microM Hg2+ and decreasing to control levels at 5 and 10 microM Hg2+. This was the result of a progressive reduction in the time to peak tension observed when HgCl2 concentrations increased. This effect probably reflects the binding of Hg2+ to SH groups inducing Ca2+ release from the sarcoplasmic reticulum. The relative potentiation of postrest contractions was used as an index of sarcoplasmic reticulum activity. It was measured after pauses of increasing duration and was reduced at concentrations of 1 microM Hg2+ when compared to that of the control. A further decrement in the relative potentiation was observed with higher Hg2+ concentrations, indicating that the activity of the sarcoplasmic reticulum was depressed by mercury in a dose-dependent manner. Tetanic contractions were also studied in the rat myocardium. The tetanic tension did not change during treatment with 1 microM Hg2+ but decreased with 5 microM Hg2+, suggesting a toxic effect on the contractile proteins only at high Hg2+ concentrations. Frog ventricular strips were studied using the same HgCl2 concentrations and no effects on either force or relative potentiation were observed. These findings suggest that Hg2+ promotes dose-dependent toxic effects on heart muscle via actions on the sarcolemma, the sarcoplasmic reticulum, and contractile proteins.
The aim of the study was to examine, in papillary muscles and in a whole heart preparation, the effects of isoproterenol on the myocardial mechanical activity at different extracellular Ca2+ concentrations. Papillary muscles from left ventricles, contracting isometrically, and rat hearts perfused by the Langendorff technique developing isovolumetric pressure at a fixed rate (200 bpm) and diastolic pressure of 5 mmHg were studied at different Ca2+ concentrations for analysis of the effects of increasing doses of isoproterenol. Papillary muscles were treated with isoproterenol (0.5 to 8 ng ml-1) at four extracellular Ca2+ concentrations (0.25, 0.5, 1.25 and 2.5 mM) and Langendorff perfused hearts were stimulated by isoproterenol (0.05 ng ml-1 to 0.8 ng ml-1), also at four extracellular Ca2+ concentrations (0.5, 1.25, 2.5 and 3.75 mM). Both papillary muscles and perfused hearts showed that force and isovolumetric systolic pressure increase in response to isoproterenol at low Ca2+ concentrations. As Ca2+ concentration is increased, isoproterenol's positive inotropic effect subsides. However, papillary muscle isometric contractions showed a similar time to peak tension decrease in response to isoproterenol at all external Ca2+ concentrations used. The results suggest that the positive inotropic response to isoproterenol, in isolated preparations, changes as a function of extracellular Ca2+ concentration decreasing as external Ca2+ increases. Time to peak tension reduction reinforces the idea that this small positive inotropic response to isoproterenol of the rat myocardium, at the physiological Ca2+ concentration, is due to the Ca2+ saturation of the mechanical activity.
1. The rat heart develops a compensatory hypertrophy after infarction which is secondary to volume overload in the left ventricle (LV) and to pressure overload in the right ventricle (RV). This study was undertaken to determine whether the reduced inotropic response to Ca2+ presented by the LV of infarcted rats extends to the RV and whether this hemodynamic profile in vivo affects the contractile performance of the ventricles assessed in vitro. 2. Male adult rats were submitted to left coronary artery ligation to produce infarction (Inf) or to a sham surgery (SO) and used 4 to 5 weeks later. The hemodynamic data were recorded in the anesthetized animals and the systolic performance of both ventricles was evaluated in vitro in the hearts perfused by the Langendorff technique. The isovolumic systolic pressure (ISP) developed by both ventricles was measured at various diastolic pressures (0 to 30 mmHg) and Ca2+ concentrations (0.62, 1.25, and 2.50 mM). 3. The RV systolic pressure was higher in Inf (N = 12) than in SO (N = 12) rats (42 +/- 5 vs 26 +/- 1 mmHg, P < 0.05). A positive and linear correlation (r = 0.86, P < 0.01) between RV systolic pressure and the RV weight to body weight ratio in Inf rats was observed. 4. Length-dependent activation, evaluated by using normalized ventricular function curves, was unchanged in the RV of Inf hearts. In the Inf LV, however, a slight improvement of the normalized systolic performance was observed in relation to SO hearts for diastolic pressures higher than 15 mmHg. 5. A similar depression of the inotropic response to Ca2+ was observed in both ventricles of Inf hearts. Moreover, for Inf hearts the increase of the ISP to Ca2+ flattened at lower Ca2+ concentrations in relation to the SO group. 6. The present results demonstrate that LV infarction in rats depresses the contractile performance of both ventricles. The reduced inotropic response to Ca2+ presented by both ventricles may contribute to the reduced capacity of the Inf heart to generate external work under conditions of higher metabolic demand.
1. The role of the sarcoplasmic reticulum (SR) in the inotropic responses produced by changes in stimulation rate and rhythm and resting tension was investigated in the rat myocardium. 2. Rat papillary muscles contracting isometrically (basic stimulation rate = 30/min) were superfused in vitro with normal Krebs solution and after addition of ryanodine (1 microM). Post-rest potentiation was obtained after pauses of 5, 10, 15, 30, 60 and 120 s, and the stimulation rate was changed from 6 to 90 bpm. Post-extrasystolic potentiation was induced by interpolating an extra stimulus after an interval of 413 +/- 15 ms. NiCl2 (2 mM) was used to confirm that contractions obtained after SR blockade with ryanodine were activated only by sarcolemmal calcium influx. 3. In the presence of ryanodine, the post-rest potentiation phenomenon disappears and the force-frequency relationship changes from the typical force decrease produced by rate increase to force increase. Under the effect of ryanodine, resting tension increased with the increase in stimulation rate. This behavior was enhanced by reducing extracellular KCl from 5.4 mM to 1 mM. This maneuver decreases Na(+)-K(+)-ATPase and increases intracellular Na+ activity, which reduces Ca2+ extrusion through the Na(+)-Ca2+ exchange mechanism. 4. SR participation in the post-extrasystolic potentiation phenomenon is also suggested because ryanodine treatment reversed the extrasystolic force depression into potentiation. In the presence of ryanodine, blockade of Ca2+ influx with NiCl2 (2 mM) abolished isometric contractions indicating that after SR blockade contractions are mainly dependent on sarcolemmal Ca2+ influx. 5. The results suggest that the SR is involved in the genesis of post-rest potentiation and contributes to the typical force-frequency relationship of the rat myocardium and to the post-extrasystolic potentiation phenomenon. Moreover, SR activity seems to be important for the maintenance of low resting tension in the cardiac muscle, which may represent a safety factor against contractures during inotropic changes produced in rate and rhythm.
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.
The effect of aluminum (Al3+) chloride (1, 5, 10, 50 and 100 microM) on myocardial electromechanical activity was studied in 10 Langendorff-perfused hearts from adult female Wistar rats. Al3+ decreased the development of isovolumic systolic pressure from 34.3 +/- 2.95 mmHg under control conditions to 11.8 +/- 1.53 mmHg at 100 microM AlCl3 (P < 0.01) (diastolic pressure = 0 mmHg). The atrial and ventricular rates also decreased, but only with AlCl3 concentrations greater than 1 microM (from 180 +/- 5 to 94 +/- 11 bpm for atrial rate and from 180 +/- 5 to 78 +/- 7 bpm for ventricular rate). Reduction of coronary flow was also observed, reaching 60% at 100 microM Al3+. A delay in atrioventricular conduction occurred at 10 microM Al3+, increasing progressively up to 100 microM (62.3 +/- 4 ms in the Al(3+)-free solution to 143 +/- 34 ms in the presence of 100 microM Al3+, P < 0.01, ANOVA). QRS duration did not change as a function of increasing Al3+ concentrations (37.1 +/- 1.7 ms in the Al(3+)-free solution vs 32.1 +/- 1.6 ms in the presence of 100 microM Al3+). No qualitative changes in ECG were observed. These data show that the toxic effects of Al3+ on the myocardium are reflected in reduced systolic pressure development and coronary flow and increased PR interval. These effects are discussed in terms of the inhibition of nucleotide hydrolysis by Al3+.
The cardiovascular effect of isoproterenol pretreatment (ISO) mimicking short duration sympathetic hyperactivity was studied in conscious adult male albino rats. Cardiac hypertrophy of right and left ventricles was observed after pretreatment with isoproterenol for 3 days (0.1 mg/kg, 3 times a day), when compared to saline-treated rats. The pressor response to noradrenaline (NOR, 1 to 1000 micrograms/kg, iv) was slightly but consistently larger in the ISO group than in the control group (in mmHg, Control = 109 +/- 3.5; NOR 1 = 114 +/- 3.3; NOR 10 = 116 +/- 4; NOR 100 = 127 +/- 5.6 and NOR 1000 = 152 +/- 7.3 for saline-treated rats and, Control = 106 +/- 5.1; NOR 1 = 112 +/- 5.1; NOR 10 = 118 +/- 5.3; NOR 100 = 134 +/- 4.9 and NOR 1000 = 162 +/- 7.5 for ISO groups). An increased reflex bradycardia was also observed in response to increasing doses of noradrenaline (in bpm, Control = 323 +/- 5.6; NOR 1 = 313 +/- 6.8; NOR 10 = 309 +/- 8.6; NOR 100 = 293 +/- 7.5 and NOR 1000 = 284 +/- 5.3 for saline-treated rats and Control = 316 +/- 4.3; NOR 1 = 294 +/- 4.3; NOR 10 = 289 +/- 3.4; NOR 100 = 267 +/- 4 and NOR 1000 = 251 +/- 2.6 for ISO groups; ANOVa, P < 0.01). There were no significant differences in autonomic tone to the heart between control and isoproterenol-pretreated animals. The present results indicate that isoproterenol treatment induces significant in vivo cardiovascular modifications.
1. Post-rest potentiation reflects basic cellular mechanisms that control cardiac muscle contraction. Transmembrane calcium influx, the Na+/Ca2+ exchange and the function of intracellular stores that liberate activator calcium upon activation are some of the mechanisms involved. 2. Three aspects of the post-rest potentiated phenomenon were investigated, using isometrically contracting rat papillary muscles and toad ventricle strips: dependence on 1) inotropic state of steady-state contractions, 2) pause duration and Na+/Ca2+ exchange activity, and 3) the extent of transmembrane calcium influx. 3. The results suggest that the potentiated state of post-rest contractions increases linearly with the inotropic state of preceding steady-state control contractions. As the pause duration increases from 5 to 240 s, the post-rest potentiation also increases, attaining a steady level after 30-s pauses. During the pause, the Na+/Ca2+ exchange mechanism operates at an activity level that can alter the amount of activator calcium used for post-rest contractions. Interventions that increase intracellular Na+, such as the increase of the stimulation rate from 0.5 to 1 Hz or the increase of extracellular NaCl concentration to 160 mM, reduce the Na+/Ca2+ activity, increasing intracellular Ca2+ and post-rest potentiation. The decrease of transmembrane Ca2+ influx during activation increases the relative participation of the sarcoplasmic reticulum in the development of post-rest potentiation. Reduction of extracellular Ca2+ concentration from 1.25 mM to 0.25 mM or the use of 1 microM verapamil and 2 mM manganese increases the relative potentiation of post-rest contractions. This is particularly observed in toad ventricle strips since post-rest potentiation, which does not develop under control conditions, is observed after verapamil or manganese treatment. The results suggest that the excitation-contraction coupling process operating for post-rest contraction activation, unlike that operating for steady-state contraction activation, depends more on the calcium stored at intracellular sites than on transmembrane calcium influx.
1. Langendorff-perfused isolated hearts and left ventricle papillary muscles from 3-month-old albino rats of both sexes were studied before and after a 30-min treatment with 17 mM urea added to the medium, a concentration equivalent to a plasma level of 100 mg/dl. To determine whether the effects observed after the addition of urea were produced by an increase in tonicity, the study was repeated using 17 mM sucrose. 2. Mechanical studies on the papillary muscles showed that isometric force development and its first time derivative decreased after washing out urea from the bath (F = 9.73 +/- 1.02 g/mm2 to 7.47 +/- 0.72 and dF/dt = 66.8 +/- 6.43 to 56.7 +/- 4.60 g (mm2)-1 s-1, respectively; P < 0.05). Inotropic responses to isoproterenol and increased extracellular calcium after urea treatment reached values similar to those obtained before urea treatment. Thus, the effect of isoproterenol and calcium was stronger than that obtained before urea treatment. 3. In Langendorff-perfused hearts, the spontaneous heart rate did not change after urea or sucrose treatment. Urea promoted a decrease in the left ventricle isovolumic systolic pressure (39.7 +/- 4.05 to 26.1 +/- 2.69 mmHg, P < 0.05) and a reduction of total QRS amplitude. 4. In both papillary muscles and isovolumic perfused hearts, contractile responses resulting from changes in extracellular sodium concentration were reduced after urea treatment. The increased osmolarity due to sucrose did not produce any changes in electromechanical activities. 5. Although 17 mM, which reduces isometric force and isovolumic pressure development and modifies the ECG, is well below the concentration required to modify protein conformation in vitro, the present results suggest that its action could be explained by an effect at the sarcolemmal level.
The effects of increasing concentrations of mercury (Hg2+) chloride (0.5, 1, 2 and 10 microM) on the myocardial electromechanical activity were studied on 10 Langendorff-perfused rat hearts. Hg2+ decreased the development of isovolumic systolic pressure from 20.3 +/- 2.13 mmHg under control conditions to 6.25 +/- 1.32 mmHg at 10 microM HgCl2 (P < 0.01) (diastolic pressure = 0 mmHg). The atrial and ventricular rates also decreased at 0.5 microM, 1 microM and 2 microM HgCl2 when compared to the Hg(2+)-free solution (from 201 +/- 4 to 126 +/- 15 bpm). However, at 10 microM Hg2+ the atrial rate increased (155 +/- 19 bpm) whereas the ventricular rate did not change significantly (119 +/- 13 bpm). A delay in atrioventricular conduction occurred at 0.5 microM Hg2+ (64 +/- 4 ms in the Hg(2+)-free solution to 91 +/- 14 ms in the presence of 0.5 microM Hg2+, P < 0.05) with no further changes at higher Hg2+ concentrations. The QRS-T duration also increased as a function of increasing Hg2+ concentrations (58 +/- 5.5 ms in the Hg(2+)-free solution to 123 +/- 15 ms in the presence of 10 microM Hg2+, P < 0.01). Qualitative changes of ECG such as extrasystoles, atrial or ventricular arrhythmias and A-V blocks were also observed. The inhibitory action of Hg2+ on ATP hydrolysis and on Ca2+ and Na(+)-K+ ATPases suggested to occur in other tissues could be the mechanism responsible for the observations reported here.
The effects of chronic propranolol (Prop) therapy on the postinfarction myocardial hypertrophy of infarcted rats were studied by histological techniques. Male albino rats were submitted to left coronary artery ligation to produce infarction or to sham surgery (Con, N = 6). Infarcted rats (Inf) were divided into 2 groups receiving Prop (2.5 mg/kg, twice a day, N = 6) or saline (N = 6) for one month, respectively. Myocyte diameters were measured in longitudinally oriented sections in the four heart chambers (60 cells/chamber). Inf produced a significant increase in mean diameter of myocytes from the right atrium and ventricle and from the left atrium. In the right ventricle, myocyte diameter increased from 8.9 +/- 0.5 microns in the Con group to 12.5 +/- 0.6 microns in the Inf group (P < 0.05). Under Prop, myocyte diameter was reduced (P < 0.05) to 9.8 +/- 0.9 microns. Similar values were observed in the right atrium. In the left atrium, Prop produced only a partial reversion of the postinfarction hypertrophy. In the left ventricle, myocyte diameter was not significantly changed after Inf or Prop therapy. These data show that beta blockers reduce the myocardial hypertrophy in the right heart chambers after experimental infarcts in rats. This effect can be secondary to reduction of pulmonary hypertension or to blockade of direct effects of catecholamines on myocardial fibers or both.
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.
Sinoaortic baroreceptor denervation (SAD) in the rat immediately produces hypertension and tachycardia, as the result of an increased sympathetic tone to the heart and resistance vessels. Adaptive processes are then installed, changing according to the duration of the SAD. In this work we studied the time course of adaptive changes occurring in the rat heart within a 30-day period. Heart rate and mean blood pressure were measured before mechanical studies in the isometrically contracting left ventricle papillary muscles. Results showed that heart rate and mean blood pressure increased immediately after the SAD. Heart rate normalized 15 days later, although hypertension persisted. Thirty days later both rate and pressure normalized. Mechanical studies showed that isometric force development (F) and its first-time derivative (dF/dt) behaved similar to controls until the 1st wk but displayed a contractile depression in the 2nd wk after SAD. However, after 30 days this depression subsided and both F and dF/dt were back to normal values. The beta-adrenoceptor responsiveness also changed during this 30-day period. Three days after denervation there was an increased sensitivity to isoproterenol action in the muscles. This sensitivity was progressively reduced as the time after denervation increased. The absence of a similar behavior with the rest-potentiated contractions suggests that these time-course adaptive changes are specific for beta-adrenoceptor stimulation.