摘要:

These studies were designed to determine the role of cerebral vascular endothelium in the “myogenic” depolarization and contraction observed in isolated cat middle cerebral arteries exposed to high transmural pressures. With intact endothelial cells we observed, on elevation of transmural pressure in cannulated isolated arteries, significant membrane depolarization, action potential generation, and reduction in internal diameter. After perfusion of the same vessels with collagenase and elastase for short periods of time to disrupt the endothelial layer, all previous responses to elevation of transmural pressure were no longer seen. Even though enzyme perfusion had no effect on membrane potential at “control” levels of transmural pressure, it abolished the pressure-dependent depolarization, action potential generation, and constriction. Furthermore, the contractile response to agonist stimulation was maintained after endothelial disruption via enzymes, showing that this method of endothelial disruption did not appreciably damage muscle cells. The data document a dependence of an intact endothelium in mediating the activation of isolated cat cerebral arteries in response to a changing transmural pressure. Thus, it is possible that the endothelial cell may serve as a transducer in the autoregulatory response to pressure.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Purified sarcolemmal and light vesicle (intracellular) fractions of β-adrenergic receptors were used to examine the effects of propranolol on receptor translocation in guinea pig heart. Guinea pigs were given propranolol (0.15 mg/kg/hr) via minipumps for 7 days and either killed or made ischemic for 1 hour via a coronary ligature. Propranolol treatment led to an externalization of β-receptors from light vesicle to sarcolemmal fractions. This externalization increased the number of surface β-adrenergic receptors that were functional, as assessed by isoproterenol-stimulated adenylate cyclase activity. After chronic propranolol treatment, ischemia did not further alter receptor distribution. These results suggest that externalization of β-adrenergic receptors from a light vesicle fraction to the sarcolemma contributes to up-regulation of β-receptors that occur in response to both propranolol treatment and ischemia. Because propranolol-treated animals show blunting in externalization after myocardial ischemia, propranolol treatment and myocardial ischemia appear to access the same pool of intracellular β-adrenergic receptors. Depletion of this pool of receptors along with receptor blockade may thus contribute to the mechanism by which the drug is efficacious in preventing some adverse effects of ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Pathogenesis of coronary artery spasm induced by histamine in miniature pigs was studied angio-graphically in in vivo and in vitro conditions. Endothelial balloon denudation was performed and the animals were fed laboratory chow for 3 months, after which coronary artery spasm was repeatedly provoked by histamine given intracoronarily. Regional hypercontraction of the coronary artery was documented by selective coronary arteriography, and the resulting myocardial ischemia was confirmed by ECG-ST changes. To evaluate coronary artery spasm without the influence of blood constituents and neural control and to quantitate the pharmacophysiological characteristics of hista-mine-induced coronary constriction in the coronary spasm, the same heart was isolated and perfused with Krebs-Henseleit solution under a constant perfusion pressure of 90 mm Hg. Histamine (10∼s M) reduced the diameter of the coronary artery of the isolated heart by 29 ± 4 and 67 ± 3% (p < 0.001) in nondenuded and denuded areas, respectively. These figures were similar to data obtained angio-graphically in vivo after the administration of histamine 10 μg/kg. The constriction of the denuded areas in response to histamine was topologically the same in vivo and in vitro. The degree of focal constriction induced by histamine, defined as a percent of stenoses from the mean diameter of the areas of proximal and distal to the spastic site, was similar in in vivo (10 μg/kg i.e.) and in vitro (10-5 M) conditions. KC1 (40 mM) reduced both the denuded and nondenuded coronary artery diameter by 67 ± 3% and 68 ± 3% (NS), respectively. The dose-response relation of the coronary diameter to histamine was not influenced by pretreatment with the nerve transmitter blockers guanethidine (3 × 10-6 M), atropine (10-6 M), and tetrodotoxin (3 × 10-7+ M). Phenylephrine (10-5 M) did not potentiate constriction of the denuded areas. In Ca+2 free solution with EGTA (2 mM), in which 118 mM KC1 did not constrict the coronary diameter, histamine (10-5 M) reduced the coronary diameter by 17 ± 2 and 19 ± 1% (NS) in nondenuded and denuded areas, respectively. Mepyramine, an Hi-receptor blocker, abolished the constrictive response to histamine. The intima was invariably thickened along the spastic portion and was coated by endothelial cells, visible microscopically. Thus, focally potentiated constriction of the coronary artery to histamine was reproducible in isolated pig hearts perfused with electrolyte solution containing 2.6 mM Ca2+. This suggests alterations in the influx of Ca2+ in the presence of H1-receptor stimulation in vascular smooth muscle of the vessel wall with intimal thickening.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The basis for the reduced maximum diastolic potential of canine cardiac subendocardial Purkinje fibers surviving one day after extensive transmural infarction was investigated, using double-barrel potassium and sodium ion-sensitive microelectrodes. The maximum diastolic potential of Purkinje fibers in infarct preparations from the left ventricular apex measured during the first hour of superfusion in a tissue bath was −50.1 ± 13.7 mV, a value markedly reduced from the value in control Purkinje fibers from noninfarcted preparations (−85.0 ± 4.5 mV). The intracellular potassium ion activity was reduced by 50.4 mM during this time (intracellular potassium ion activity equals 61.6 ± 16.1 mM, as compared to control intracellular potassium ion activity of 112 ± 19.8 mM). The potassium equilibrium potential was reduced by 16.0 mV (from −97.2 ±4.7 mV in controls to −81.2 ± 6.9 mV), thus accounting for about one half of the reduction in the maximum diastolic potential. After 6 hours of superfusion, the maximum diastolic potential increased to − 78.9 ± 8.7 mV (still significantly less than control). The potassium equilibrium potential had largely recovered (− 93.8 ± 5.9 mV). The intracellular sodium ion activity of Purkinje fibers in the infarcts (15.6 ± 6.9 mM) was elevated during the first hour of superfusion by 6.2 mM compared to control (9.4 ± 2.6 mM), and this was only 12% as much as the initial intracellular potassium ion activity decrease. Sodium ion activity after 3–6 hours of superfusion was not significantly different than normal (12.1 ± 4.9 mM). In conclusion, only a portion of the maximum diastolic potential changes can be explained by a reduction of the potassium equilibrium potential. It is likely that change(s) in the cell membrane sodium-potassium pump's function and in the membrane conductance are also involved. Furthermore, the lack of a compensatory increase in intracellular sodium ion activity accompanying the large reduction of intracellular potassium ion activity may be a consequence of the cellular acidosis, which is known to occur during myocardial ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Right coronary autoregulation was assessed in 14 open-chest, anesthetized dogs. In Group 1 (n = 5), the left common and right coronary arteries were cannulated and perfused independently. As coronary perfusion pressures varied simultaneously between 70 and 120 mm Hg, right coronary blood flow changed by 48%, whereas left coronary flow changed by 13%. In this pressure range, the autoregula-tory closed-loop gain of the right coronary circulation averaged 0.37 ± 0.01, reflecting a modest autoregulatory capability but significantly less than that of the left coronary circulation, 0.78 ± 0.08. In Group 2 (n = 9), only the right coronary artery was perfused, and right coronary venous blood was collected for determining arteriovenous oxygen extraction. Autoregulatory gain was similar to that of Group 1, indicating that collateral flow associated with intercoronary pressure gradients does not mask right coronary autoregulation. Right ventricular myocardial oxygen consumption varied directly with perfusion pressure, ranging from 7.1 ± 1.0 to 2.9 ± 0.8 ml O2/min/100 g as pressure was reduced from 160 to 40 mm Hg. Thus, right coronary autoregulation is masked by an opposing change in oxygen demand. When right ventricular oxygen consumption was altered by pacing, a linear flow-oxygen consumption relationship was observed (8.2 ± 0.4 ml/min/100 g per ml CVmin/lOO g). Subtraction of flows associated with pressure-induced changes in metabolism revealed a potential autoregulatory capability of the right coronary circulation similar to that manifested by the left coronary circulation.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The purpose of this study was to determine whether thyroid state affects the beat-to-beat regulation of contractile strength in cardiac muscle. Transmembrane action potential and isometric force were simultaneously recorded in right ventricular papillary muscles from euthyroid, hypothyroid, and hyperthyroid rats. Large thyroid state-dependent alterations in the contractile response of the muscles were not accompanied by any significant difference in the action potential. During steady-state stimulation, single test stimuli were interpolated at varying intervals. Action potential duration and peak force of the test responses were plotted against the test stimulus interval to produce electrical and mechanical restitution curves. In all muscles studied, electrical and mechanical restitution followed different time courses; over a wide range of test intervals, action potential duration and peak force of the test responses changed in opposite directions. Thyroid state profoundly affected the recovery of contractile strength, while only minor differences were found among the electrical restitution curves of the three groups of preparations. Mechanical recovery was much faster in hyperthyroid and slower in hypothyroid than in euthyroid muscles. We conclude that electrical and mechanical restitutions occur through separate processes and that the thyroid state affects only the mechanisms responsible for the contractile recovery of rat myocardium. The modifications induced by thyroid dysfunction on contractile recovery might be accounted for by an effect of thyroid state on a time-dependent recycling of calcium by the sarcoplasmic reticulum.

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

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID