Pharmacological evidence for catecholamine-independent contractile effects of X-537A on the isolated working rat heart preparation

1979 ◽  
Vol 57 (4) ◽  
pp. 428-431 ◽  
Author(s):  
Robert L. Rodgers ◽  
Joanne I. Moore ◽  
K. Roger Hornbrook

The ionophore X-537A increased heart rate and contractility of the isolated, working rat heart preparation. The increased heart rate appeared to be caused solely by release of catecholamines as the response was completely eliminated by reserpine pretreatment or addition of propranolol to the perfusate. The inotropic response, however, had an apparent catecholamine-independent component as neither propranolol, nor propranolol in combination with phentolamine, completely eliminated the inotropic response to X-537A. On the other hand, reserpine pretreatment did abolish the inotropic effect of the ionophore but this action appeared to be a nonspecific one as the responses to norepinephrine and to CaCl2 were substantially diminished.

1986 ◽  
Vol 250 (6) ◽  
pp. H923-H931 ◽  
Author(s):  
L. G. Lelievre ◽  
J. M. Maixent ◽  
P. Lorente ◽  
C. Mouas ◽  
D. Charlemagne ◽  
...  

The inotropic effect of ouabain on cardiac hypertrophy was evaluated on an isolated Langendorff rat heart preparation with performances registrated by means of an intraventricular balloon. These effects were compared with the drug action on the sarcolemma-bound Na+-K+-ATPase activity. On both normal and pressure-overload induced hypertrophied rat hearts (ventricular wt-to-body wt ratios of 2.1 and 3.3, respectively) the inotropic effect of ouabain (10(-9)-10(-4) M) was evaluated at 0.25 mM external Ca2+. Compared with normal hearts, the recovery of a normal contractile function after the inotropic response was significantly slower in hypertrophied hearts. This was valid with the two protocols applied. During a 30-min washout period, the inotropic response remained nearly unchanged in hypertrophied hearts, whereas it was almost completely reversed in control groups. Sarcolemmal vesicles from both heart groups exhibited high Na+-K+-ATPase activities (sp. act.: 105 +/- 16 mumol X h-1 X mg-1). In both normal and hypertrophied cardiac sarcolemmal preparations, the Na+-K+-ATPase was heterogeneous, with high- and low-sensitivity forms. Their relative proportion was two-to-one. In both heart groups, their respective apparent affinities for ouabain were similar (inhibitory concentration of 50% = 10(-8) and 10(-6) M, respectively). The release of ouabain from these two sites was measured, in washout experiments, by the rates of enzyme relief from inhibition. High- and low-sensitivity forms in hypertrophied heart preparations released ouabain at seven- and threefold lower rates, respectively, than the corresponding forms present in normal cardiac sarcolemmal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)


1996 ◽  
Vol 150 (3) ◽  
pp. 487-495 ◽  
Author(s):  
M Toth ◽  
P Taskinen ◽  
H Ruskoaho

Abstract Relaxin, a reproductive hormone of the insulin-like growth factor family, increases heart rate in experimental animals but its other actions on cardiac function and cellular mechanisms responsible for the positive chronotrophic effect remain unknown. We have studied the actions of human recombinant gene-2 relaxin on the release of atrial natriuretic peptide (ANP) and cardiac function (heart rate, contractile force, perfusion pressure) as well as the underlying signal transduction mechanisms by using the isolated perfused spontaneously beating rat heart preparation. The administration of relaxin into the perfusion fluid at concentrations of 1·5, 3 or 10 nm for 30 min caused a dose-dependent sustained increase in heart rate, while contractile force and perfusion pressure remained unchanged. In addition, infusion of relaxin at a concentration of 10 nm into the perfusate produced a gradual 1·5-fold increase in immunoreactive ANP (IR-ANP) secretion (from 456 ± 76 to 701 ± 124 pg/ml, F=4·5, P<0·001). The ANP secretory and chronotrophic effects of relaxin appear to involve the activation of protein kinase C, since administration of a protein kinase C inhibitor staurosporine at a concentration of 30 nm completely blocked the effect of relaxin (10 nm) on IR-ANP secretion P<0·001) and heart rate (P<0·001). A cAMP-dependent protein kinase inhibitor, H-89 (100 nm), also substantially reduced the ANP secretory effect of relaxin and attenuated the increase in heart rate during the sustained phase of the relaxin infusion (P<0·001). KN-62 (3 μm), a Ca2+/calmodulin-dependent protein kinase inhibitor, decreased the positive chronotrophic effect of relaxin (P<0·001) but did not influence significantly the effect of relaxin on IR-ANP release in isolated perfused rat heart preparation. These results provide the first evidence that relaxin stimulates the secretion of ANP from isolated perfused rat hearts. Our results also suggest that relaxin modulates ANP secretion by activation of protein kinase C and cAMP-dependent protein kinase pathways. Journal of Endocrinology (1996) 150, 487–495


1992 ◽  
Vol 71 (2) ◽  
pp. 127-131 ◽  
Author(s):  
Shlomo A. Ben-Haim ◽  
Haim Ben-Ami ◽  
Gal Hayam ◽  
Uri Taitelman ◽  
Yeouda Edoute

1992 ◽  
Vol 54 (5) ◽  
pp. 915-920 ◽  
Author(s):  
Todd L. Demmy ◽  
George J. Magovern ◽  
Race L. Kao

1961 ◽  
Vol 39 (1) ◽  
pp. 9-13
Author(s):  
V. W. Adamkiewicz

Insulin-Zn (40 units/kg, s.c.) prolongs two- to four-fold the cardiac action of the glycoside k-strophanthin (10–20 mg/kg, s.c. or i.p.) in the rat (100–200 g) as reflected by the duration and intensity of the heart rate deceleration (E.C.G.). Insulin also increases six times the mortality in rats overdosed with k-strophanthin (30 mg/kg i.p.), but simultaneously prolongs the duration of survival. On the other hand, insulin appears not to affect the cardiac action of the aglycon strophanthidin.


1991 ◽  
Vol 59 (4) ◽  
pp. 1053-1068 ◽  
Author(s):  
J. Wondergem ◽  
A. Van Der Laarse ◽  
F.J.M. Van Ravels ◽  
A.-M. Van Wermeskerken ◽  
H.R. Verhoeve ◽  
...  

Sports ◽  
2019 ◽  
Vol 7 (5) ◽  
pp. 107
Author(s):  
Filipe Manuel Clemente ◽  
Pantelis Theodoros Nikolaidis ◽  
Thomas Rosemann ◽  
Beat Knechtle

The purpose of this study was to compare internal and external load measures during two regimens (6 x 3’ and 3 x 6’) of a 5 vs. 5 format of play. Moreover, within-regimen changes (between sets) were also tested. Ten amateur soccer players (age: 19.8 ± 1.6 years; experience: 8.3 ± 2.1 years; height: 177.4 ± 3.8 cm; weight: 71.7 ± 4.2 kg) participated in the experiment. Internal load was measured using the CR-10 scale as the rated of perceived exertion (RPE) scale and a heart rate (HR) monitor. The measurements of total (TD), running (RD) and sprinting (SD) distances were also collected using a 10-Hz validated and reliable GPS. Comparisons between regimens revealed that the 3 x 6’ regimen was significantly more intense in terms of RPE than the 6 x 3’ regimen (p = 0.028; d = 0.351), although no significant differences were found in HR. Significantly greater averages of TD (p = 0.000; d = 0.871) and RD (p = 0.004; d = 0.491) were found in the 6 x 3’ regimen. In both regimens, the RPE was significantly lower during the first set than in the remaining sets. On the other hand, the TD was significantly shorter in the last sets than in the earlier. In summary, the present study suggests that shorter sets may be beneficial for maintaining higher internal and external load intensities during 5 vs. 5 formats, and that a drop-in performance may occur throughout the sets in both regimens.


1982 ◽  
Vol 242 (1) ◽  
pp. H89-H93
Author(s):  
M. M. Bersohn ◽  
K. I. Shine ◽  
W. D. Sterman

Perfusates containing high magnesium concentrations have been suggested to have a protective effect for ischemic myocardium, but the mechanism for such an effect is unclear. We investigated the recovery of isolated perfused rabbit and rat hearts from ischemia under varied conditions of increased Mg. Hearts were made ischemic in the presence of normal 1.2 mM Mg or elevated 15 mM Mg. Rabbit hearts, which show minimal alteration in contractility in the presence of 15 mM Mg, were not protected from ischemia by high Mg perfusate. Rat hearts, which have a large negative inotropic response to 15 mM Mg, exhibited significantly better recovery of mechanical function following ischemia in the presence of high Mg than following ischemia with normal Mg. This protective effect was abolished by increasing both Ca and Mg in the perfusate to prevent the decline in contractility that normally occurred with Mg. Reperfusion with 15 mM Mg after ischemia also had no protective effect if the rat heart had been made ischemic in the presence of normal Mg. We conclude that elevated Mg protects ischemic myocardium only under circumstances in which it has a negative inotropic effect before the onset of ischemia, i.e., in the rat heart perfused with normal Ca. These results suggest that the mechanism of protection by high Mg involves sparing of ATP. However, the different responses to Mg of the species studied in these experiments should be a caution against extrapolating such results from rat hearts to other species.


1976 ◽  
Vol 54 (4) ◽  
pp. 618-621 ◽  
Author(s):  
Chris P. Bolter ◽  
John R. Ledsome

The inotropic and chronotropic responses to dobutamine (DBA) and isoprenaline (ISO) were examined in eight chloralose anaesthetised dogs. Following acute cardiac denervation, heart rate (HR) and contractility (dP/dtmax), measured at a fixed paced atrial rate, were recorded during intravenous infusion of incremental doses of DBA and ISO. Both DBA and ISO elicited increases in HR and dP/dtmax. The increases in dP/dtmax for a one beat per minute increase in HR was 102.0 ± 10.6 mm Hg/s (1 mm Hg (0 °C) = 133.322 Pa), during DBA infusion, and 61.5 ± 8.4 mm Hg/s during ISO infusion. It appeared that the relatively greater inotropic effect of DBA in comparison with ISO was the result of an augmentation of its inotropic activity. DBA infusion was accompanied by a significant increase in mean aortic pressure at all doses examined. An increase in afterload may account for part of the increased inotropic response to DBA.


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