ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

To determine if cardiac tissue is capable of modulating its response to a stimulating hormone, we studied desensitization to the positive inotropic effect of catecholamines on embryonic chick ventricular tissue using a phase contrast microscope-video motion detector system and correlated the contractility findings with concurrent observations of β-adrenergic receptor properties and aden-ylate cyclase activity. Incubation for 30 minutes with μIM isoproterenol produced a diminution in the subsequent inotropic response to 0.1μIM isoproterenol to 35± 8% (mean± SEM) of the initial response. This desensitization to the positive inotropic effect of isoproterenol was catecholamine-specific and was not accompanied by alteration in the inotropic response to Ca2+. To investigate the mechanism of desensitization, we studied properties of the β-adrenergic receptor in homogenates of chick embryo ventricle using [3H]dihydroalprenolol as a ligand. Thirty minutes of incubation with 1 pM isoproterenol produced no change in β-adrenergic receptor density (92.8 ± 5.1 fmol/mg protein) and only a small change in receptor affinity (KD= 5.2± 0.3 DM VS. 7.0± 0.3 nM;P< 0.01). Receptor affinity for isoproterenol, as judged by [3H]dihydroalprenolol displacement, was not changed significantly. The adenylate cyclase stimulation by isoproterenol in similarly prepared tissue, however, was reduced to 29% of the control value after 30 minutes of exposure to 1 /IM isoproterenol. Adenylate cyclase sensitivity was restored by guanosine 5'-(β,γ-imino)triphosphate. Thus, desensitization of physiological respon-siveness of ventricular tissue to a β-adrenergic agonist was accompanied by little change in β-adrenergic receptor properties but by marked diminution in adenylate cyclase responsiveness. These observations suggest that uncoupling of the β-adrenergic receptor-adenylate cyclase complex may be the mechanism of short-term desensitization of ventricular muscle to the positive inotropic effects of isoproterenol.Circ Res 47: 493-501,1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

To explore the mechanisms underlying the shortening of the cardiac action potential in hypoxia, we studied the effect of hypoxia on the ionic currents in cat papillary and trabecular muscles using the single sucrose gap-voltage clamp technique. For potentials positive to −70 mV, hypoxia induces an increase in time-independent outward current. The changes in the tail current suggest that time-dependent outward current is not increased but, rather, reduced. Because the time course of IK remains unchanged, we concluded that the shortening of the action potential is not a result of a change in the time-dependent outward current. In the potential range of the plateau, the amplitude of the slow inward current is not affected by hypoxia. Its time constant of inactivation appears slightly decreased. The prolongation of the action potential by epinephrine during hypoxia is accompanied by an increase in the slow inward current. As a result of these studies, we conclude that the shortening of the cardiac action potential in the early stage of hypoxia results from an increase in K+outward background current.Circ Res 47: 501-508, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Cardiovascular and respiratory effects of intra-left atrial or intra-left ventricular injec-tion of serotonin were studied in conscious dogs (n = 8), anesthetized closed-chest dogs (n = 13) and anesthetized open-chest dogs(n= 9). Serotonin (50-200 /ig), injected as a bolus, resulted in an initial bradycardia and hypotension followed by a delayed tachycardia and hypertension in the conscious dogs. The hypertension was seen as an increase of 21.5 ± 2.7 (mean ± SE) nun Hg from a control pressure of 102.5 ± 1.9 mm Hg, whereas the initial decrease in pressure was 22.6 ± 1.9 mm Hg. The tachycardia was 23.3 ± 3.9 beats/min above a control heart rate of 104.9 ± 3.9 beats/min whereas the bradycardia was 58.5 ± 3.7 beats/min below control. There was a significant attenuation of the hypotension in both groups of anesthetized dogs. In fact, no hypotension was elicited in the open-chest anesthetized dogs. Open-chest anesthetized dogs showed only a hypertensive response (mean increase 67.2 ± 5.5 mm Hg). Stimulation of respiration was seen in all groups of dogs. In conscious dogs there was a 214.8 ± 15.4% increase in respiratory depth and a 20.8 ± 3.1 breaths/min increase in respiratory rate. Atropine significantly reduced the bradycardia and abolished the hypotension in conscious dogs. Bilateral cervical vagotomy did not abolish the response in open-chest anesthetized dogs. We conclude that the so-called "hypertensive coronary chemoreflex" is altered dramatically by the state of the preparation and by anesthesia.Circ Res 47: 509-515, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We studied the effects of graded hypoxia on mechanical performance of cardiac ventric-ular muscle by producing controlled, stepwise decreases in partial pressure of oxygen (Po2) in the medium bathing the kitten papillary muscle preparation and in the perfusate of the Langendorff-prepared rabbit heart. For kitten papillary muscle at 30°C and with stimulation rate at 30/min, maximum rate of contraction (+dT/dtmM) and maximum rate of relaxation (-dT/dtm.*) were 184 ± 10 inN/mm2per sec and 162 ± 12 mN/mm2per sec, respectively, during control conditions with Po2at 634 ± 7 mm Hg. Step decreases in Po2from 634 mm Hg produced decreases in steady state -dT/dtmu, that were significantly greater than corresponding decreases in +dT/dtma», except at the lowest Po2. When Po2(mm Hg ± SE) was 411 ± 10, 218 ± 4, and 92 ± 3, steady state +dT/dtmMvs. -dT/dt-, (expressed as%of pre-hypoxia control value ± SE) were: 97 ± 4 vs. 85 ± 7, 76 ± 5 vs. 59 ± 6, and 47 ± 5 vs. 28 ± 4, respectively. When the lowest Po2of 34 ± 6 mm Hg was achieved, considerable shortening of the duration of the mechanical cycle occurred, and values for +dT/dtm«x and -dT/dtma, (expressed as % of pre-hypoxia control value ± SE) of 28 ± 7 and 21 ± 7, respectively, were not significantly different. Graded hypoxia similarly affected left ventricular isovolumic pressure developed by the coronary perfused rabbit heart. In both preparations, changes in relaxation relative to changes in contraction during progressive hypoxia were biphasic: decreases in maximum relaxation rate were disproportion-ately greater than decreases in maximum contraction rate with intermediate hypoxia, but the proportionality was restored when severe hypoxia produced a decrease in cycle duration.Circ Res 47: 516-524, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Electrical measurements of current flow in ventricular myocardium immersed in silicone oil showed that angiotensin II increases the cell-to-cell spread of current within seconds. The increases in current spread and conduction velocity occur without any changes in resting membrane potential or maximum rate of rise of the action potential. The concentration range was 10 nM to 10 μIM, with an ED50of 100 DM for angiotensin exposures lasting about 10 seconds. The largest effects were an apparent decrease in resistance through the cellular pathway to 50% of control and a 40% increase in conduction velocity, which returned to control in about 15 minutes. Continuous or repeated exposure to angiotensin caused desensitization to appear. These effects were found with or without denervation by 6-hydrox-ydopamine and β-adrenergic blockade by 1 μM propranolol in calf, pig, sheep, and rabbit ventricular myocardium. Therefore, angiotensin appears to increase electrical conduction rapidly and directly in cardiac muscle by decreasing resistance through the cellular pathway.Circ Res 47: 524-529, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Selective autonomic blockade with propranolol, atropine, and combined atropine and propranolol was used to elucidate the role of the autonomic nervous system in the cardiovascular responses that occur during voluntary static exercise in conscious cats. Seven animals were operantly conditioned to hold a bar against a fixed resistance for a constant time of 15 seconds and were then placed on an exercise regimen which consisted of small weekly increments in resistance. With a resistance of 100 g, heart rate (HR) increased by 7%. With exercise at a resistance of 200 g, HR (10%), left ventricular systolic pressure (LVSP, 16%), and LV max dp/dt (18%) increased, and significant changes in these parameters persisted throughout the remainder of the training period. β-Adrenergic receptor blockade with propranolol abolished the increase in LV max dp/dt, whereas HR and LVSP increased. After atropine, the increase in HR was abolished at the early training stages, whereas LVSP and LV max dp/dt increased. Administration of atropine and propranolol blocked the increase in HR and LV max dp/dt responses, whereas LVSP increased. In this study, the increased HR in response to exercise was mediated primarily by the parasympathetic nervous system, whereas the increases in LV max dp/dt were mediated by the sympathetic nervous system. Furthermore, the bradycardia accom-panying chronic performance of isometric exercise resulted from both an increase in vagal tone and a decrease in sympathetic tone.Circ Res 47: 530-535, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Abdominal aortic constriction in rats results in mild cardiac hypertrophy (20% increase in left ventricular weight compared to sham-operated controls) which is associated with increased numbers of β-adrenergic receptors (123 ±7.3 ftnol/mg protein (mean ± SE) VS. 87 ± 4.3 ftnol/mg in controls,P< 0.01) without changes in their affinities for dihydroalprenolol. In vitro synthesis of phosphatidylcholine through successive methylation of phosphatidylethanolamine by S-adenosyl-L-methionine is enhanced in the hypertrophied myocardium (0.38 ± 0.03 nmol/mg per 30 minutes vs. 0.23 ± 0.03 nmol/mg per 30 minutes in controls,P< 0.01). In both experimental groups, methyltransferase activity has a high affinity for S-adenosyl-L-methionine (Km= 6.8 μM), depends on Mg2*, is optimal around pH 9.0, and is inhibited by S-adenosyl-L-homocysteine (Ki = 8.3 μM). The possible relationship between phospholipid methylation and changes in myocardial β-adrenergic receptors was studied in both normal and hypertrophied hearts. Preincubation of cardiac membranes with S-adenosyl-L-methi-onine increased the numbers of β-adrenergic receptors in proportion to the duration of incubation and the concentration of S-adenosyl-L-methionine. In both groups, S-adenosyl-homocysteine, but not 5'-AMP or L-methionine, attenuated the increase in β-adrenoreceptors. These results indicate that phos-pholipid methylation may be an important mechanism for regulation of β-adrenergic mechanisms in both normal and hypertrophied myocardium.Circ Res 47: 536-541, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Lidocaine has been reported to be more depressant in ischemic than normal myocardium. To determine the influence of pH on the electrophysiological effects of lidocaine, we recorded trans-membrane potential and dV/dtmulfrom guinea pig papillary muscles mounted in a single sucrose gap. Recovery kinetics of dV/dtma, were studied by introducing progressively early premature responses during phase 4 at a drive rate of 0.5 Hz. In Krebs-Henseleit solution (HCO3− = 25 mM, CO2= 5%, pH 7.4), lidocaine (1.5 x 10−5M) did not significantly change action potential characteristics. The recovery time constant (T) of dV/dtmaxwas increased from 10 ± 4 (mean ± SD) to 91 ± 12 msec. In the presence of lidocaine, T increased from 91 ± 12 to 212 ± 5 msec when the extracellular pH (pHo) was lowered by increasing the [CO2] to 20% (HCO3− = 25 mM, pHo= 6.95). Similarly, when pHowas lowered by decreasing [HCO3−] (HCO3− = 7.5 mM, CO2= 5%, pHo= 6.95), T increased from 96 ± 11 to 185 ± 41 msec. However, if the [CO2] was increased to 20% while the pHowas maintained at 7.4 [HCO3− = 85], T was unchanged compared to a [CO2] of 5%. Drug-free solutions of pHo= 6.95 (CO2= 5% or 20%; HCOr = 7.5 or 25 mM) did not increase T. The increase in T with a decrease in pHowas greater than that predicted by a change in distribution of the drug across the membrane. These data are consistent with the view that local anesthetics bind to a receptor in the sodium channel thereby inactivating it. The process of recovery from inactivation during the resting state occurs by exit of uncharged drug through the membrane. The degree of protonation of receptor-bound drug is increased by extracellular acidosis. This decreases the proportion of drug that may leave the receptor via the membrane and hence causes a slowing of the recovery from inactivation.Circ Res 47: 542-550, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

To test whether the pressure-volume relationship of the canine small intestinal vascula-ture is linear over the normal range of portal venous pressures (5 to 35 nun Hg), we used two methods to measure volume: (1) the integral of inflow minus outflow (IFD), and (2) tissue activity of5lCr-labeled erythrocytes (Cr-51). Venous pressures were changed in steps of 5 mm Hg with a servo-controlled system. The tissue was perfused at a constant rate. With venous pressures of 3.6 to 38.6 mm Hg, the vascular compliance was 2.19 ± 0.42 (SD) ml/kg − mm Hg using IFD, and 1.87 ± 0.50 ml/kg-mm Hg using Cr-51. Although a quadratic term significantly improved the fit, the effect was small (less than 3 ml/kg with a 30 nun Hg venous pressure change). The control blood volume of the intestinal loop at a venous pressure of 8.6 ± 1.5 (SD) nun Hg was 86.2 ± 19.1 ml/kg tissue weight using the mean transit time of a step input of indocyanine green at a perfusion pressure of 106 ± 29 nun Hg and a flow of 556 ± 147 ml/ruin − kg. We conclude that there is no significant change in compliance over the normal venous pressure range of 5-35 nun Hg.Circ Res 47: 551-558, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID