摘要:

The effects of chronic dynamic exercise on myocardialβ-adreneegic and muscarlnlc cholinergic receptors and chronotropic sensitivity to isoproterenol were studied in 5 Yucatan mlniswine. Right atrial and left ventricular biopsies, heart rate responses to isoproterenol, and maximal exercise treadmill testing were obtained before and after 10–19 weeks of treadmill running. Radioligand studies using125I-iodocyanopindolol (ICYP) and3H-quinuclidinyl benzilate (QNB) were used to determine the number ofβ-adrenergic and muscarinic cholinergic receptors. Maximal oxygen consumption increased from 52 ± 5 to 65 ± 7 ml/kg/min (mean ± SD;p<0.02), maximal workload from 530 ± 111 to 1,074 ± 179 KPM/min (p<0.01), resting heart rate decreased from 91 ± 13 to 62 ± 4 beats/min (p<0.01), heart rate at 75% of pretraining maximal workload decreased from 253 ± 15 to 196 ± 12 beats/min (p<0.01), and maximal exercise heart rate decreased from 273 ± 6 to 254 ± 9 beats/min (p<0.01). Decreased heart rate responsiveness to adrenergic stimulation was observed following chronic exercise. Maximal isoproterenol-stimulated heart rate decreased from 225 ± 13 to 185 ± 28 beats/min (p< 0.05) and the slope of the isoproterenol dose-response relation decreased from 63 ± 16 to 40 ± 16 (p<0.05). Radioligand studies revealed a decrease inβ-receptor number in the right atrium following chronic exercise (61 ± 9 vs. 34 ± 8 fmol/mg;p<0.02), but receptor number in membranes from the left ventricle did not change (60 ± 9 vs. 62 ± 4 fmol/mg). There was no change in muscarinic cholinergic receptor number in right atrial membranes following the training period (204 ± 73 vs. 230 ± 92 fmol/mg). Thus, chronic dynamic exercise results in down-regulation ofβ- adrenergic receptors in the right atrium and is associated with reduced chronotropic responsiveness to exercise and isoproterenol stimulation.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Left ventricular pressure-flow relations were studied, using excised working rabbit hearts and imposing constant flow ejections (flow-clamps) to separate the effects of flow on pressure from those of time, flow duration, starting volume, ejected volume, and volume at specified time. Pressure-flow data at given volume and time were independent of flow duration, starting volume, and ejected volume for flow-clamp durations exceeding 30 msec. Flow history independent of pressure-flow relations was linear for flow values larger than ± 5 ml/sec. The time-varying elastance model, E(t), of the ventricle was extended with a resistive component. Transient effects of flow can be explained by including a second elastance. The resulting verified 3-component model is consistent with recent reported experimental findings. The properties of internal resistance correspond to a constant unloaded ejection flow Qmax which was tested by extrapolating the linear pressure-flow relations to zero pressure. Qmax reached a plateau value of approximately 25 ml/sec within 50 msec after the start of contration. In relaxation, Qmax is only slightly smaller. Qmax did not depend on volume; therefore, the following equation was adequate for the relation between pressure, p(t); volume, V(t); and flow Q(t), during the flow-clamped ejections from 30 minutes after the start of the flow: (t) = E(t)±(V(t) - Vd)±(l - QW/Qmax)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We examined the importance of decreased heart rate in the beneficial effect ofβ-adrenergic blockade on exercise-induced regional myocardial ischemia and contractile dysfunction in conscious dogs with single vessel coronary stenosis (ameroid constrictor). Studies were performed during control treadmill exercise, which produced regional myocardial ischemia (blood flow measured with microspheres) and wall dysfunction (measured using sonomicrometers). A second run was performed after the administration of atenolol (0.3–1.0 mg/kg i.v.), and the reduced heart rate caused by atenolol during early steady-state running was then prevented by atrial pacing during the latter portion of the run. Atenolol reduced the exercise heart rate from 217 ± 25 beats per minute (SD,n= 9) to 166 ± 15, and ischemic zone wall thickening during systole improved from 27 ± 22% of the resting value in the control run to 50 ± 25% of the resting value in the atenolol run (p<0.01). Atrial pacing then increased heart rate to 217 ± 23 beats per minute, and regional wall thickening deteriorated to 15 ± 25% of the resting value. Regional subendocardial blood flow in the ischemic zone during atrial pacing with atenolol was slightly less than that observed in the control run, in both ischemic and control zones, indicating no remaining beneficial effect of atenolol when heart rate reduction was eliminated. We conclude that the only significant mechanism for the improvement in exercise-induced ischemia and wall motion produced by atenolol is a reduction in the exercise heart rate. Furthermore, when the heart rate decrease was prevented, regional blood flow and function tended to be more depressed after atenolol than during the control run.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We investigated the hemodynamic effect of synthetic atrial natriuretic factor Auriculin A (ANF) and its influence on arterial baroreflex control of heart rate, systemic blood pressure, and perfuslon pressure in the hind limb (perfused at constant flow) in rabbits anesthetized withα-chloralose and urethane. The neural mechanisms underlying these effects were also studied. In the intact animal, a 45-minute constant infusion of ANF (2 μg/kg prime, 0.2 μg/kg/min) significantly reduced mean blood pressure and increased mean perfusion pressure, while heart rate did not change. Comparable data were obtained with lower (0.5 μg/kg + 0.05 μg/kg/min; 1 μg/kg + 0.1 μg/kg/min) or higher (4 μg/kg + 0.4 μg/kg/min; 8 μg/kg + 0.8 μg/kg/min) doses of ANF. In addition, ANF enhanced brady-cardic reflex responses to phenylephrine i.v. bolus administration, while it did not change baroreflex-mediated responses to nitroglycerin i.v. bolus administration and to 30-second bilateral carotid occlusion. The specificity of the influence of ANF on arterial baroreflex responses was confirmed by the observation that no significant change in reflex responses to phenylephrine or carotid occlusion was detectable during a comparable decrease in blood pressure induced by a constant infusion of nitroglycerin. Bilateral vagotomy prevented both the fall in blood pressure and the increase in perfusion pressure induced by ANF, while cholinergic blockade (atropine, 0.5 mg/kg i.v.) or adrenergic blockade (propranolol, 0.3 mg/kg i.v. + phentolamine, 0.3 mg/kg i.v.) did not modify the hemodynamic response to ANF observed in the Intact animal. The ANF-induced enhancement of the reflex bradycardic response to phenylephrine-induced rise in blood pressure was prevented by both vagotomy and atropine. In conclusion, our data suggest that in this experimental model an increase in parasympathetic tone is involved in the blood pressure lowering effect of synthetic ANF as well as in the potentiation of the reflex bradycardie response to phenylephrine-induced arterial baroreceptor loading caused by the peptide.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The dynamic mechanical behavior of excised rabbit papillary muscles that had been tonically activated by replacing bathing Ca2+with Ba2+was studied. Steady activation was used to visualize the dynamic behavior of cardiac myofilaments more clearly than is possible during twitches, which are complicated by the kinetics of excitation-contraction coupling. To avoid artifacts due to damaged ends of the muscle, the length of a central segment, which was denned by 2 tungsten pins inserted through the muscle, was measured. To test the mechanical behavior of the contractured muscles (at 24°C), the central segment length was sinusoidally oscillated (amplitude 1%) at 15 different frequencies (0.05–30 Hz). The dynamic stiffness of the central segment was calculated from the ratio of force response amplitude to length perturbation amplitude. At low frequencies (below 0.4 Hz), stiffness was approximately constant and reflected the force-length relation. However, in a localized range near 1 Hz, there was a distinct drop in the magnitude of dynamic stiffness to approximately half its low-frequency baseline. This range may reflect the dynamics of attachment and detachment of force generators. The frequency of minimum stiffness was consistent among all muscles (1.3 ± 0.3 Hz). Moreover, no significant change in this frequency was found over the examined range of lengths (90–100% of the segment length that produced maximal developed force) and activation levels (Ba2+ concentration 0.3–1.0 mM). From 2 to 8 Hz, dynamic stiffness appeared to reflect force-velocity properties, but at higher frequencies, another elastic property emerged. At 30 Hz, stiffness was proportional to force, with an apparent series elasticity less than 1.8%. Even though the muscles had only moderate longitudinal inhomogeneity, quantitatively significant (35%) errors would have been introduced had the study relied on total muscle length instead of central segment length.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The dynamic stiffness of excised cardiac muscles that would be likely to have different intrinsic speeds of contraction, as judged by previous biochemical reports of their myosin ATPase rates, was compared. This study included muscles from thyrotoxic rabbits and newborn rabbits, rabbit atria, and normal papillary muscles at different temperatures. The usual excitation-contraction coupling process was bypassed by replacing bathing Ca2+with Ba2+. The ensuing actively maintained contracture allowed us to focus more specifically on the contractile properties of the myofilaments. Dynamic stiffness was determined by sinusoidally oscillating muscle length at many different frequencies over the range 0.05–50 Hz while holding average muscle length at 95% of the systolic length, thus giving maximal developed force. The form of the stiffness modulus spectrum was similar for all muscles studied: stiffness was fairly constant at low frequencies, decreased to a minimum at an intermediate frequency, and then increased steeply, followed by a milder rate of increase over high frequencies. Differences in contraction speed were evident by shifts in the frequencies at which corresponding portions of the stiffness spectrum appeared. The clearest landmark was the frequency where stiffness became minimum (fmin). This varied strongly with temperature (Q10= 2.9). Compared to normal adult papillary muscles (fmin= 1.2 Hz), fmin. was 2.2 times faster in thyrotoxic myocardium, 1.9 times faster in 1-week-old rabbits, and 3.7 times faster in atrial trabeculae. These ratios of functional speed are similar to the corresponding ratios of myosin Ca2+-ATPase activities reported in the literature.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Human angiotensinogen cDNA clone was isolated from a liver cDNA library using a 32-nucleotide-long, synthetic oligonucleotide The cDNA insert was 1,030 bp long and coded for the secretory and biologically active angiotensin II regions of the angiotensinogen molecule The RNA from rat liver, brain, and heart was analyzed by the Northern hybridization procedure using nick translated angiotensinogen cDNA as a probe In addition to liver, the angiotensinogen mRNA is present in the brain and the heart The angiotensinogen mRNA in the heart is at least fourfold to fivefold more abundant as compared with the liver We also provide evidence that angiotensinogen mRNA is present in the rat atria and right ventricle but not detectable in the left ventricle The size of the angiotensinogen mRNA is the same from all three of the tissues, as judged by their electrophoretic mobilities

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The relation between smooth muscle membrane potential and contractile force was investigated in the rat tail artery to assess the importance of smooth muscle depolarization in the control of smooth muscle tone. Smooth muscle membrane potential and contractile force were measured simultaneously in isolated pieces of rat tail artery exposed to a range of concentrations of norepinephrine, 5-h1ydroxy-tryptamine, or raised external potassium. Potassium caused depolarization and contraction when the membrane was depolarized beyond -40 mV. Maximum contraction occurred at -19 mV, and farther depolarization gave no increase in contraction. Both norepinephrine and 5-hydroxytryptamine caused contraction and depolarization, but the relation between depolarization and contraction was not the same as when potassium was used. There was significant contraction when the membrane potential was more negative than - 50 mV, and the membrane potential was around -30 mV during maximal contractions. Although they acted on pharmacologically different membrane receptors, the relation between membrane potential and contraction was the same for norepinephrine and 5-hydroxytryptamine. Prazosin reduced the responses to norepinephrine but did not change the relation between membrane potential and contractile force. These results indicated that norepinephrine and 5-hydroxytryptamine binding to their respective receptors might activate the same sets of intracellular processes that subsequently caused both depolarization and contraction.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID