ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

The substrate specificity of tonin from rat submaxillary gland was examined with a series of synthetic peptides encompassing the C-terminus of the decapeptide substrate angioten-sin I. In contrast to angioteosin I-converting enzyme from plasma or lung, only angiotensin I, (des-Asp1)-angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I are substrates of tonin with Kmvalues of 34.5 &mgr;M, 39.3 &mgr;M, and 54.4&mgr;M, respectively, while the shorter C-terminal peptides are not hydrolyzed. Thus, the N-terminal sequence extending from position 1 to 3 is the enzymatic binding site for tonin. Turnover numbers of 33.4 sec-1, 42.8 sec-1, and 6.5 sec-1are observed for the hydrolysis of angiotensin I, (des-Asp1)- angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I, respectively. The relative percentage rates of hydrolysis (proportional to V/Km)at low substrate concentrations ([S] << Km) are almost identical for (des-Asp1)-angiotensin I, angiotensin I, and the tetradecapeptide substrate, indicating that these three peptides are equally good substrates at low physiological concentrations. The observed high specificity of the enzyme lends support to the possible important role of tonin for local conversion in tissue. The conversion of (des-Asp1)-angiotensin I to (des-Asp11)-angiotensin II (angiotensin III) is of particular interest in relation to the recently suggested, potential role of the latter peptide in aldosterone release.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

Serial measurements of cardiac output (CO), mean arterial pressure (MAP), heart rate, and total peripheral resistance (TPR), were made on unanesthetized rabbits with previously implanted Doppler flowmeters. After 2 days of control measurements tbe rabbits were subjected alternatively to bilateral renal cellophane wrapping (wrap group) or to sham operation and additional measurements were made 1, 2, 4, 8, 16, 25, and 32 days after operation. During the 1st week after operation changes in CO were identical in tbe wrap and sham-operated groups, with an overall increase to a value of 110% of control on day 4 (P< 0.05). Thereafter CO fell gradually, reaching 75% of control by day 32 in the wrap group, but only 95% of control in the sham-operated group. When CO was expressed per unit of body weight tbe latter differences were somewhat reduced, but still were significant. In wrap animals MAP and TPR rose progressively to 155% and 194% of control by day 32. In the sham-operated group the corresponding increases to 108% and 118% of control were significantly smaller. The MAP and TPR of the renal wrap rabbits exceeded the values in sham-operated rabbits, even over the 1st week after operation, by an average for MAP of 8.6 ± 1.4% (P< 0.001), and for TPR of 8.0 ± 2.5% (P. 0.01 (.There-suits suggest that the changes in CO during the 1st week were a nonspecific consequence of the preceding wrap or sham operation. They bore no apparent relationship to the subsequent deielopment of tbe hypertension which was "resistance-mediated" from the earliest stages. We conclude that the present findings for the rabbit differ from those reported for other species and do not conform to tbe changes predicted by the autoregulation theory of the pathogenesis of hypertension.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

We studied the uptake of labeled dexamethasone (2H-Dex) or methylprednisolone (2H-MP) in isolated perfused cat hearts during the first hour of acute myocardial ischemia. Considerable amounts of2H-Dex and2H-MP were taken up by toe plasma membrane (F1) fraction in control, border zone, and ischemic myocardial tissue. Lesser amounts were incorporated into the remaining cell fractions. A gradient of glucocorticoid uptake was observed that decreased from control tissue to ischemic tissue in all subcellular fractions (i.e., F1to F5). Accordingly, supernatant fraction (S) to particulate (P) ratios of labeled glucocorticoid uptake increased from control to ischemic tissue, indicating that myocardial cell damage resulted in a decrease in glucocorticoid-binding capacity in subcellular fractions obtained from ischemic tissue. The activity of S'-nucleotidase (5'ND), a plasma membrane marker in myocardial cells, also decreased from normal to ischemic tissue. Furthermore, we found that uptake of2H-MP and2H-Dex was associated with toe retention of 5'ND activity in F1fractions of both border zone and ischemic tissue. Similar protection of plasma membrane integrity occurred in the supernatant fraction as determined by changes in S/P ratios of 5'ND activity. These data provide support for the concepts that (I) plasma membrane changes occur soon after acute myocardial ischemia, and (2) the mechanism by which glucocorticoids exert a protective effect in myocardial ischemia may be related to membrane stabilization.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

We evaluated hyperthermic influences on ische-mic hearts by comparing two groups of intact working swine hearts (n = 20) made globally iscbemic. Heart muscle temperature was selectively increased from 37.5 ± 0-3°C to 39.7 ± 03°C in one group (n= 11) by warming the coronary perfusate. Ischemia in nonnotbermic hearts significantly (P< 0.05) decreased mechanical function (as reflected by increases in left ventricular end-diastolic pressure [LVEDP]), myocardial oxygen consumption (MVO,), glucose uptake, glycoktic flux, free fatty acid (FFA) uptake and oxidation, and tissue stores of high energy phosphates. Heating in iscnemic hearts further depressed mechanical function at similar reductions in coronary flow and MVO2. Glucose uptake was terminally increased over nonnotbermic values (329 vs. 221 &mgr;mol/hr per g), as was glycolytic metabolism, FFA uptake (26 vs. 17 /&mgr;mol/hr per g), and FFA oxidation (21 vs. 11 &mgr;mol/hr per g). However, these changes were not translated into increased energy stores of tissue creatine phosphate and ATP. Thus, in ischemic hearts, hyperthermia neither prevented the development of mechanical deterioration nor improved oxidative phospborylation despite increases in metabolic substrate utilization. These data suggest that in experimental global ischemia beat is an added energy drain in already burdened myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

We investigated changes in circumflex, left anterior descending (LAD), and right coronary artery flows as well as changes in collateral flows to these vessels after long-term circumflex occlusion. Coronary and collateral flows of each vessel were determined simultaneously in an isolated heart preparation in which the vasculature was maximally dilated with dipyridamole. The resistances as related to total heart weight of the circumflex, LAD, and right coronary arteries of 16 control dogs were found to be 0.59 ± 0.06, 0.93 ± 0.09, and 237 ± 0.17 (mean ± sem) mm Hg/[(ml/min)/100 g], respectively. Total minimal coronary resistance was 0.21 ± 0.01. In 10 dogs subjected to occlusion for 1 month no significant change in circumflex coronary resistance was observed, but the resistance of the unimpaired vessels decreased significantly. The resistances of the LAD and right coronary arteries were 0.66 ± 0.04 and 1.72 ± 0.13, respectively. Both values were considerably less (P< 0.01) than control. In nine dogs subjected to occlusion for 3 months the resistance of the unimpaired LAD and right arteries, as well as the circumflex coronary resistance, were not significantly different from control. We also found that retrograde flows for all vessels increased 7-fold after 1 month and 10.5-fold (relative to control) after 3 months of ocdusion. From these data we conclude that vascular adaptations, which occurred in response to an ischemic stimulus, are responsible for the long-term regulation of the metabolic needs of the myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

We studied antegrade concealed conduction of alrial extrastimuli (A2) that blocked in the atrioventricular (AV) node in eight subjects, using a third extrastimulus (A3), coupled at decreasing coupling intervals to A2. Three A,-A2intervals were tested in each subject: late (just shorter than AV nodal effective refractory period), intermediate, and early (just longer than atrial functional refractory period). The curves relating the following variables were constructed for each A2: A11-A3, H1-H3and A2-A3, A3-H3. The former was compared to the control A1-A2, H1-H2curve. Concealment of A2was demonstrated in all eight subjects at the three tested values of A1-A2. The A1-A3, A3-H3curve allowed analysis of AV nodal conduction time (A3-H3) and AV nodal recovery time (defined as the shortest A2-A3at which the impulse conducted to the His bundle) at identical values of A2-A3. In all subjects the timing of blocked A2nad minimal effect on both AV nodal conduction time and recovery time. In five of the eight subjects a late A2sporadically conducted to the His bundle. Conduction of A, to the His bundle resulted in marked lengthening of both AV nodal conduction and recovery times. Concealed conduction of A2was always demonstrated, but the degree of concealment was relatively fixed, whether A2was an early, intermediate, or late blocked premature beat. Slow conduction of A2had a much greater effect than concealment of A2on subsequent impulse conduction.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

To elucidate the role of arterial baroreceptors in the acute regulation of arterial pressure in the conscious animal, arterial pressure was lowered and raised in intact, conscious dogs, and in dogs after bilateral section of both carotid sinus and aortic nerves (total arterial baroreceptor denervation, TABD). Pressure was altered by intravenous bolus injections and continuous infusions of nitroglycerin and methoxamine and also by hemorrhage. TABD resulted in a change in peak mean arterial pressure 2–4 times as great as that seen in intact dogs following injection of nitroglycerin or methoxamine. However, when the time taken for the arterial pressure disturbance to return to control levels, as well as the absolute change in arterial pressure, was considered (the pressure-time product), responses of dogs with TABD were far greater for nitroglycerin (7–9 times that seen in intact dogs) and methoxamioe (11–15 times). Arterial pressure responses of dogs with selective section of the carotid sinus nerves were intermediate but closer to those of intact dogs than to dogs with TABD. With infusion of drugs or following hemorrhage, responses of mean arterial pressure were 3- to 5-fold greater in dogs with TABD than in intact dogs, indicating that the static open loop gain of the arterial baroreceptor system ranged from2to 4.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

We made separate measurements of angiotensin II (A II) and of its immunoreactire metabolites (2–8 heptapeptide, 3–8 bexapeptide, and 4–8 pentapeptide) in arterial and venous plasma from subjects with widely different plasma levels of the peptides. A II and its three metabolites were extracted from blood, separated by paper chromatography, and measured by radioimmunoassay using an A II antisemm which had a 100% cross-reaction with each metabolite. In contrast to results of previous studies, A II was found to predominate in both arterial (60–100%) and venous (55–100%) blood. The biologically active 2–8 beptapeptide metabolite accounted for only 10% of the activity in arterial plasma. Radioimmunoassay of venous plasma extracts using an A II antisemm which had a low cross-reaction with the 3–8 hexapeptide and the 4–8 pentapeptide confirmed the results obtained using the antisemm which had a 100% cross-reaction with the metabolites. We conclude that radioimmunoassay methods for measuring A II in venous blood may be more accurate and relevant than has previously been recognized. The small difference between A II concentrations in arterial and venous plasma suggests further that there may be significant conversion of angiotensin I (A I) to A II in the limb vasculature.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

The extracellular and intracellular potassium (K+) actitivies of isolated superfused rabbit atrial muscle wtre measured using K+-sensitive liquid ion exchanger microelectrodes. When the pH of the bathing medium was decreased from 7.5 to 6.8. intracellular K+activity fell and extracellular K+activity rose from a mean control level of 3.6 mm to a new steady state level of 3.9 mM after I hour. When the pH was further decreased to 6.1, extracellular Inactivity increased to a mean of 4.9 mM. Following the change in pH, the increase in extracellular K+activity occurred over a period of 30-40 minutes at which time a stable talue was reached and maintained for the next hour. On return to normal pH the extracellular K+activity returned to control with a time constant of 20 minutes or less. Measurements of infracellular K+activity over 1 hour showed a mean loss of 3 mM at pH 6.8, and a mean loss of 8 mM at pH 6.1. The loss was reversible within 20 minutes of return to control pH. The increase in extracellular K+activity was accompanied by a decrease in resting membrane potential as well as decreases in maximum dv/dt and overshoot of the action potential. The action potential contour underwent complex changes consisting of decrease in the plateau and a prolongation of the time to full repolarization.

ISSN:0009-7330    

出版商:OVID    

年代:1976

数据来源: OVID