ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

To study the influence of acute and chronic angiotensin-converting enzyme blockade on the pressor response to exogenous angiotensin II, vasopressin and norepinephrine, we gave normal female Wistar rats 100 mg of captopril or 1 ml of 5% glucose twice daily by gavage for 2 weeks. On the 15th day, rats were anesthetized with pentobarbital, and dose-response curves to angiotensin II, lysinevasopressin, and norepinephrine were obtained before and after intraperitoneal injection of 100 mg/kg of captopril or 1 ml of 5% glucose. Acute as well as chronic converting enzyme blockade enhanced the pressor response to exogenous angiotensin II. Similarly, sensitivity to exogenous vasopressin was increased by both acute and chronic converting enzyme inhibition. In contrast, chronic converting enzyme blockade significantly blunted the response to exogenous norepinephrine, whereas acute blockade tended to accentuate its pressor effect. These results suggest that chronic angiotensin- converting enzyme blockade may partly inhibit sympathetic activity which, in turn, might contribute to the antihypertensive efficacy of this therapeutic approach. These results also point to an important physiological interaction between the two pressor hormones, angiotensin II and vasopressin.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The inward current (“oscillatory current”) which may be present after the end of a depolarizing clamp was studied in sheep cardiac Purkinje fibers by means of a voltage-clamp method. The following results were obtained. In order to appear, the oscillatory current (Io<) requires a previous depolarization to = −20 mV or beyond and a repolarization to = −40 mV or to more negative potentials. The I0requires a minimum duration of the depolarizing clamp and becomes larger with longer clamps. With repolarization to more negative potentials (= 90 mV), Io. becomes smaller and may disappear. Also, Io, can be triggered twice if the potential is clamped to two different levels in succession. By several procedures which modify the other known currents (fast Na+current, slow inward current, early outward current, plateau current Ixi and pacemaker current), it can be demonstrated that Io. is not due to their oscillatory behavior and can occur in the absence of any one of them. Interventions which increase the contractile force presumably by increasing intracellular calcium stores enhance the Io» or may make it appear. In fact, these interventions may extend the voltage range over which Io» appears. These interventions include lowering potassium, increasing calcium, trains of depolarizing clamps, and administration of norepinephrine and of strophanthidin. It is concluded that I0» is a physiological event which is enhanced by certain procedures, and it appears to be of much importance in drive-induced arrhythmias under different conditions.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Anesthetized dogs were studied to characterize the renal hemodynamic response to acute, transient hypoxemia and to determine the role of renal prostaglandins (PGE and PGF) in that response. Acute hypoxemia of 10 minutes duration (mean arterial Po232 ± 9 torr) induced a reversible increase in renal blood flow (RBF) (measured by electromagnetic flow probe) and mean arterial pressure (MAP) with a decreased urinary flow rate (V) and no change in glomerular filtration rate (GFR) or renal vascular resistance (RVR). Urinary excretion of PGE (UPGE) and PGF (UPGF) (measured by radioimmunoassay) was not significantly changed by hypoxemia under these conditions. After inhibition of the prostaglandin system by administration of indomethacin (5 mg/kg) or meclofenamate (5 mg/kg) intravenously, a significant decrease in RBF and GFR with an increase in RVR occurred in response to hypoxemia. Furthermore, there was a significantly greater decline in URGE and UPGF with hypoxemia after prostaglandin inhibition than before treatment. Control (non-drug treated) animals demonstrated no difference in response to a second episode of hypoxemia relative to the first hypoxemic response. The significant changes in URGE (ΔUPGE), UPGF (ΔUPGF), and GFR with hypoxemia after treatment were not secondary exclusively to a decline in RBF, as shown by the similar response of ΔUPGE and GFR to hypoxemia in dogs in which RBF was enhanced with hypoxemia after treatment by means of an adjustable aortic clamp. Inhibition of prostaglandin synthesis, therefore, unfavorably altered the ability to maintain normal renal perfusion and function during acute hypoxemia in these animals. This renal response to hypoxemia may be mediated by decreased renal prostaglandin production under these conditions.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Studies from this laboratory have shown that the border of a 24-hour canine infarct is histologically sharp and is composed of numerous interdigitating peninsulas of necrotic and normal tissue. To see if this sharp boundary is spatially related to the capillary beds of occluded and non- occluded arteries, the left anterior descending artery (LAD) was ligated in five mongrel dogs. Twenty- four hours later, white silicone rubber (Microfll) was injected into the LAD distal to the ligature; simultaneously and under the same pressure, red Microfil was injected into the left main coronary artery (LMCA). In hematoxylin and eosin sections from the border of the infarct, capillaries supplied by the LAD (white) were either in areas of necrosis, in normal epicardium or, rarely, in normal tissue along the lateral boundary; those supplied by the LMCA (red) were almost always in normal regions. Quantitative evaluation of this relationship revealed that the majority of the vessels in the normal and necrotic tissue were concordant (i.e., that normal tissue was supplied by the LMCA, and necrotic tissue by the LAD). However, a small zone of vascular discordance, averaging approximately 30 /im in width, was present along the infarct boundary, possibly representing a narrow border zone of little conse- quence. Hence, the complex interdigitation of normal and necrotic tissue in the lateral border of an infarct is predominantly a function of the interdigitation of the capillary beds supplied by the occluded and nonoccluded arteries.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

I studied the role of calcium in the activation of isolated rings of saphenous and basilar arteries of the rabbit by comparing the effect of calcium withdrawal with the effect of the calcium antagonist nimodipine [isopropyl(2-methoxyethyl)-l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyr- idinedicarboxylate]. Serotonin-induced contractions of both vessels were inhibited quickly by incubation in calcium-free solution, showing the contractions of both vessels to be dependent on extracellular calcium. Potassium-induced contractions of both vessels were inhibited markedly by nimodipine (basilar: ID50= 1.7 × 10∼10mol/liter; saphenous: ID50= 2.6 × 10∼′° mol/liter), showing depolarization- induced calcium influx (probably through “potential sensitive channels”, PSCs) to be sensitive to nimodipine. In the basilar artery the sustained, tonic phase of serotonin-induced contractions (probably through “receptor operated chennels,” ROCs) was potently inhibited (ID50= 7.3 × 10∼10mol/liter) by nimodipine. However, the initial short-lived phase of this contraction of the basilar artery was relatively unaffected (IDao = 2 × 106mol/liter), indicating that the inhibitory action of nimodipine on tonic contractions of the basilar artery was not due to antagonism at the serotonin receptor level. In contrast, in the saphenous artery the serotonin-induced contractions were unaffected by nimodipine in doses up to 2.4 × 10∼5mol/liter. It is postulated that the selective inhibition of the sustained tonic contraction of the basilar artery is due to a selective inhibition by nimodipine of calcium movement through ROCs in this vessel. Agonist-induced activation of ROCs in peripheral blood vessels does not seem to be affected by calcium antagonists.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

To determine the basis for age-related changes that occur in the transmembrane action potentials (AP) of canine cardiac Purkinje fibers (PF), we used standard microelectrode techniques to study PF from normal neonatal and adult beagles. As previously shown, neonatal PF AP have a less negative maximum diastolic potential (MDP), a lower AP amplitude (amp) and maximum upstroke velocity of phase 0 (Vmax), and shorter AP duration measured at 50% and 100% repolarization than have those of adults. Further, the termination of phase 1 and the peak of phase 2 occur at more positive levels of membrane potential in neonatal PF. The less negative MDP in neonatal PF is associated with a lower intracellular potassium activity (aK′) as demonstrated with a K+-sensitive microelectrode. Neonatal PF showed greater depression of AP amp and Vmaxduring superfusion with the rapid Na+channel blocker, tetrodotoxin (TTX), than did adult PF. The attainment of more negative voltages at the termination of phase 1 in adult compared to neonatal PF was not attributable to age-related differences in response to changes in drive cycle length, temperature, or external Cl” concentration. However, 4-aminopyridine, a blocker of the early, repolarizing potassium current, altered this variable in adult and not in neonatal PF. The effects of verapamil and AHR-2666, both slow inward current blockers; of TTX, which blocks a background inward Na+current; and of TEA+, which blocks repolarizing K+current, were studied on AP repolarization. Adult PF AP were more sensitive to the effects of AHR-2666, verapamil, and TEA* and less sensitive to the effects of TTX than neonates.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The aortic wall is nourished by diffusion from the aortic lumen and from vasa vasorum in the adventitia and outer layers of media. Intimal proliferation in atherosclerosis might be expected to reduce the effectiveness of diffusion from the lumen and increase dependence on nourishment by vasa. This study was performed to determine whether there is increased perfusion of the aortic wall by vasa vasorum in atherosclerosis. We used microspheres to measure flow through vasa in normal and atherosclerotic cynomolgus monkeys. Blood flow to inner layers of the thoracic and abdominal aorta was less than 1 ml/min × 100 g in normal monkeys, and there was a minimal increase in atherosclerotic monkeys. Flow to the outer layers of the thoracic and abdominal aorta was 1.3 ± 0.9 and 2.2 ± 0.8 ml/ min per 100 g in normal monkeys. Flow to outer layers of the thoracic and abdominal aorta was increased in atherosclerotic monkeys to 17 ± 8.9 and 31 ± 12 ml/min per 100 g (P< 0.05 vs. normal). Thus there is increased perfusion of the atherosclerotic aorta, particularly in the outer layers. During maxima] vasodilation induced by infusion of adenosine, flow through vasa was 3- to 8-fold greater in atherosclerotic than in normal monkeys. This finding suggests that proliferation of new vessels, rather than dilation of existing vessels, accounts for the increase in blood flow through vasa. We speculate that hyperemia of the aortic wall in atherosclerosis may be in part a compensatory response to increased oxygen requirements and possibly to ischemia produced by intimal proliferation and a resulting increase in diffusion distance.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Stimulus-response curves of aortic baroreceptors constructed by alternately increasing and decreasing pressure from a normal baseline or set-point differ from curves constructed by varying pressure in one direction only from an abnormally high or low pressure. In anesthetized dogs we recorded impulses from aortic baroreceptors with myelinated fibers, using a pressurized reservoir to control mean aortic blood pressure (MABP). After setting MABP to a baseline of 100 mm Hg (normal MABP in unanesthetized dogs), we constructed baroreceptor response curves by alternately decreasing MABP from 100 to 30 mm Hg, and increasing it from 100 to 180 mm Hg, in each case returning MABP to the baseline to obtain hysteresis loops. All baroreceptors were active at 100 mm Hg, their discharge averaging 15–16 impulses/sec. At all pressures above threshold, baroreceptors fired more when pressure was increasing than when pressure was decreasing. This hysteresis caused the steepest part of the response curve constructed in this manner to span the baseline value, demonstrating that, contrary to previous views, aortic baroreceptors signal decreases in pressure below the normal level, as well as increases above it. We also constructed response curves after holding MABP at a “hyperten- sive” baseline of 125 mm Hg for 20 minutes. “Hypertensive” curves demonstrated reversible resetting, shifting significantly to the right of “normotensive” curves so that baroreceptor threshold increased on average by 7 mm Hg (P< 0.01). Both hysteresis and short-term resetting probably result from the viscoelastic behavior of wall elements with which baroreceptors are coupled.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Cardiac sympathetic afferent fibers activated during coronary occlusion exert an excitatory influence on sympathetic discharge to the heart in cats after spinal cord section. The significance of this cardiocardiac sympathetic reflex response during myocardial ischemia in animals with an intact neuraxis is unknown. We studied the responses of efferent cardiac sympathetic nerve activity (CSNA), arterial pressure, and heart rate to coronary occlusion in two groups of dogs with cardiac sympathetic reflexes intact and with other reflex inputs affecting CSNA sectioned or controlled. In group I (n = 10), the vagi were sectioned, the spinal cord remained intact, and the carotid sinuses were isolated and perfused to maintain baroreceptor input constant. Coronary occlusion was performed at moderate and low basal levels of CSNA by setting carotid sinus pressure at 125–150 and 200 mm Hg, respectively. Under these conditions, CSNA was not altered by occlusion of either the anterior descending or the circumflex coronary artery. In group II (n = 4), the vagi were sectioned and the spinal cord was interrupted. In these dogs, CSNA increased significantly (61 ± 19%) during coronary occlusion. These results show that an excitatory cardiocardiac sympathetic reflex can be demonstrated in dogs with spinal cords sectioned but not with spinal cords intact. This finding is consistent with the view that inhibitory bulbospinal pathways minimize the influence of the spinal cardiocardiac sympathetic reflex during myocardial ischemia in anesthetized dogs.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID