摘要:

In view of evidence implicating thyrotropin-releasing hormone (TRH) as a chemical mediator of synaptic transmission onto spinal sympathetic neurons, this peptide was administered intrathecally, in a dose of 6.5 nmol, at the T9 and T2 spinal levels in the anesthetized rat. At the lower thoracic level TRH increased arterial pressure and heart rate; these effects peaked at 4–7 minutes and decayed over the next 15–20 minutes. At the upper thoracic level the pressor and cardioacceleratory responses were roughly similar in time course but were smaller in magnitude. Hexamethonhim (10 mg/kg i.v.) was tested on the responses from the lower thoracic level; both pressor and cardioacceleratory responses persisted after hexamethonium pretreatment. In addition, intravenous administration of 6.5 nmol of TRH failed to alter arterial pressure or heart rate, suggesting that the effects produced by the intrathecal administration of TRH were doe to an action of the peptide in the spinal cord. The results also indicate that the pressor effect and the increase in heart rate may be mediated in the sympathetic ganglia at least partly via nonnicotinic transmission. Our results provide physiological support for the possibility that TRH is a chemical mediator of synaptic transmission onto sympathetic preganglionic neurons. This study indicates that the functional sympathetic pathways utilizing TRH as a chemical mediator include those regulating arterial pressure and heart rate.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The reversibility of functional and structural microvascular alterations in chronic renal hypertension has not been established. Twelve weeks after surgery to induce hypertension, in vivo arteriolar and venular dimensions were measured in the cremaster muscle of rats with one-kidney, one-clip hypertension (1K1C), rats in which the clip was removed after 8 weeks (1KNT), and controls. Systolic Mood pressure was significantly elevated after 3 days in 1K1C rats and reached a plateau by 6 weeks. In 1KNT rats, systolic blood pressures were similar to 1K1C rats but were normalized 1 day after unclipping. A marked medial-intimal hypertrophy was found by histological techniques in the thoracic and abdominal aortae (45% and 69%, respectively) but not in cremaster feeding arteries of 1K1C rats. These arterial changes were reversed after unclipping. In 1K1C rats, medial-intimal area decreased in first- through fourth-order (1A, 2A, 3A, and 4A) arterioles along with a decline in relaxed diameter (41%, 30%, 20%, and 21%, respectively), which was only partially restored after unclipping. Heart weight was increased by 67% in 1K1C rats, but it did not differ between 1KNT and controls. Therefore, the reversal of chronic renal hypertension can normalize gross structural alterations in the heart and large vessels, but more time may be required to normalize completely the arteriolar changes. These data indicate that long-term structural adaptations in renal hypertension are different in arterioles and arteries, and they may be related to chronic changes in blood flow and/or pressure.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The ionic mechanisms of amantadine-induced changes in membrane potential and automatic activity in guinea pig ventricular myocytes were studied using the suction-pipette whole-cell clamp method. While 25-100 μM amantadine decreased the action potential amplitude and duration, 200 and 400 μM amantadine lengthened the action potential duration and decreased the maximum diastolic potential with an appearance of diastolic depolarization and automaticity. In the presence of 25-100 μM amantadine, the preparations developed an afterpotential due to incomplete repolarization and a delayed afterdepolarization that eventually brought about triggered automaticity. The former type of afterpotential was abolished by tetrodotoxln (TTX) and the latter by Co2+. Spontaneous activity from the diastolic depolarization was also abolished by Co2+but not by Cs+. Amantadine suppressed the calcium current to as much as half of the control at the concentrations used (25-200 μM). The drug also produced a depression of the inward rectifier K+current. The outward current showing time-dependent decay was activated at the plateau voltages by concentrations lower than 100 μM, whereas the delayed outward K+current was depressed by the drug in a concentration-dependent manner at more positive potentials. Amantadine activated the TTX-sensitive and TTX-insensitive inward currents on repolarization from depolarized states, without producing the transient inward current. These results indicate that the amantadine-induced diastolic depolarization and afterpotentials are caused by changes in multiple ionic currents and that, therefore, the drug can be used as a unique model for the study of arrhythmogenesis.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of extracellular acidosis on contraction of single isolated ventricular cells from rabbit was measured in a system in which pH0could be changed in < 200 msec The contractile response to acidotic levels was complete within 25 seconds. The response was measured 30 seconds after pH0was decreased to 7.0, 6.5, 6.0, and 5.5 at each of 8 [Ca]0levels (0.125–4.0 mM). Cell shortening versus [Ca]0was plotted to construct a curve for each pH0level, with each point relative to shortening at pH 7.5, [Ca]0=l mM (100% value). Calcium current (1 mM [Ca]0) was also measured 30 seconds after pH0was decreased from 7.5 to 6.5 with single-cell patch clamp technique. The contractile response to extracellular acidosis is accurately predicted by assuming two (probably sarcolemmal) sites at which H+ions affect calcium binding and/or flux: Contractile shortening = 1/[antilog (pK-pH)] + 1 × shorteningmax· [Ca]0/Kd+[Ca]0The first factor represents a set of sites that are proposed to control access, dependent on the degree of their ionization, to sites represented by the second factor. The latter sites are proposed to accept calcium according to mass-action law. The response of calcium channel current to extracellular acidosis was also complete and reversible within 25 seconds. The current response indicates that the two-site model could be predictive for the effect of extracellular acidosis on calcium current in ventricular cells.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The presence of a neurogenic vasodilator mechanism was investigated in isolated bovine mesenteric arteries (BMAs) that were precontracted with phenylephrine. Electrical field stimulation induced tetrodotoxin-sensitive relaxations in guanethidine-pretreated BMAs. The relaxation occurred after a delay of about 5-8 seconds and amounted to 25-35% in different sets of experiments. The relaxation was not affected by classical receptor antagonists such as atropine (1 μM), cimetidine (3.9 μM), clemastine (2.8 μM), naloxone (1.2 μM), 8- phenyltheophylline (1 μM), propranolol (3.4 μM), ritanserin (5 μM), or droperidol (13 μM). The nicotinic acetylcholine-receptor stimulant l,l-dimethyl-4-phenyl-piperazinium iodide (10 μM) was without effect on the relaxation, and removal of the endothelium of the arteries also had no effect. The bee venom component apamin (1 μM), which has been shown to block the nonadrenergic, noncholinergic relaxation in intestinal and vascular smooth muscle from other species, was also found to be without effect on the relaxation induced by electrical field stimulation in BMAs. Pretreatment of the arteries with capsaicin (1 μM) had no effect per se and did not affect the relaxation induced by a subsequent stimulation. Capsaicin has been suggested to release neurotransmitter and eventually deplete neurons containing substance P and calcitonin gene-related peptide. Furthermore, exogenously applied calcitonin gene-related peptide (1-100 nM), substance P (10 nM-1 μM), and vasoactive intestinal peptide (0.3-30 nM) gave relaxations amounting to less than 10%. It is postulated that electrical field stimulation induces a neurogenic relaxation of a nonadrenergic, noncholinergic nature in BMAs. The relaxation is not dependent on an intact endothelium and seems not to be mediated by any of the known vasodilatory neuropeptides.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Heat production during and after contraction of isolated rabbit papillary muscles was measured at 20°C with metal-fllm thermopiles. Under control conditions (0.2 Hz, pH 7.4) total heat and steady-state force production due to 120 twitches were 1.0 ± 0.4 J/g and 29.5 ± 5.1 mN/mm2(mean ± SD;n=5), respectively. Increasing the CO2of the bicarbonate-buffered superfusate from 5% (pH 7.4) to 24% (pH 6.6) led to a decrease of force and heat production, 54% and 72%, respectively, of the control value. The recovery heat-time constant, reflecting the time course of oxidative phosphoryiation, increased from 23.0 ± 5.1 seconds at pH 7.4 to 69.5 ± 34.7 seconds at pH 6.6. The ratio of recovery and initial heat equaled 1.06 under both conditions. Enhancing the metabolic rate by increasing the stimulation frequency to 1.0 Hz led, after an initial maximum, to a decline of force and heat presumably as the consequence of shortage of oxygen in the muscle core. The recovery phase in this case was characterized by a double exponential function having time constants of 7.6 and 64.4 seconds. When pH was lowered to 6.6 together with the enhancement of the stimulation frequency to 1 Hz, an additional exothermal process, unrelated to force production, was observed during contraction and for some time thereafter. It was concluded that severe acidosis slows down the rate of oxidative phosphoryiation and may reduce the economy of contraction. However, it does not change the nature of recovery and initial heat processes. These data suggest the possible mechanism of an additional exothermal process occurring at a high stimulus frequency and low pH.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The present studies were designed to investigate the interaction between activated polymorphonuclear neutrophils (PMNs) and endothelial regulation of vascular smooth muscle function. Rabbit peritoneal PMNs(4xl03-4xl05cells/ml) added to muscle bath chambers containing phenylephrine-precontracted rabbit isolated aortic rings produced no effect on vascular tone. However, when PMNswere activated with the chemotactic peptide, f-met-leu-phe (0.1 μM), PMNsproduced concentration-dependent vascular contraction, which was dependent on the presence of the endothelium. Aortic rings denuded of endothelium were unaffected by activated PMNs. Superoxide dismutase (100 units/ml) treatment of tissues blocked completely PMNinduced vascular contraction, whereas mannitol (20 mMj had no significant effect on PMNinduced vascular contraction. Pyrogallol (a generator of superoxide anion) produced a response that was similar to that observed with activated PMNs. Superoxide anion production was measured separately, and the time of peak rate of superoxide anion production corresponded to the time of the maximal vascular contractile responses. Activated PMNs added to vascular tissues undergoing endothelium-dependent relaxation mediated by either acetylchollne or A23187 produced a reversal of vascular relaxation. Furthermore, activated PMNsdid not have any effect on endothelium-independent vascular relaxation produced by either isoproterenol or nitroglycerin. The present Investigation reveals that activated PMNs can release superoxide anion and produce endothelium-dependent contraction. The endothelium-dependent contraction may be the result of superoxide anion inactivation of endothelium-derived relaxing factor.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The cardiovascular effects of arginine vasopressin (AVP) administered into a lateral cerebral ventricle or into the cisterna magna were investigated in conscious Long Evans (control) rats and AVP-deficient Brattleboro rats. The effects of subpressor intracerebroventricular and intracisternal doses of AVP on cardiac baroreflex sensitivities were also determined. Intracerebroventricular and intracisternal AVP increased blood pressure of both strains of rat in a dose-dependent manner. The maximum pressor response produced by intracerebroventricular AVP in Long Evans rats was 13 ± 2/13 ± 1 mm Hg (systolic/diastolic,n=6) after 100 ng AVP. The pressor response to the highest intracerebroventricular dose of AVP tested in Brattleboro rats (30 ng) was 46 ± 13/21 ± 6 mm Hg (n=6). Intracerebroventricular AVP caused a tachycardia in Brattleboro rats but had no effect on heart rate of Long Evans rats. At doses greater than 1 ng, the increases in blood pressure produced by intracisternal AVP in both groups of rats were significantly greater than the increases produced by the same doses given intracerebroventricularly. Heart rate fell in a dose-dependent manner after intracisternal AVP in Long Evans rats but not in Brattleboro rats. Cardiac baroreflex sensitivities of Brattleboro rats were not significantly different from those of Long Evans rats and were not modified by intracerebroventricular (0.3 ng) or intracisternal (0.1 ng) AVP. In Long Evans rats, intracisternal AVP (0.3 ng) increased cardiac baroreflex responses to both increases and decreases in pressure. Intracerebroventricular AVP (0.3 ng) increased the sensitivity of the reflex in response to an elevation but not to a reduction in blood pressure. These results suggest that Brattleboro rats are more sensitive than Long Evans rats to the central pressor action of AVP and indicate that AVP can modify the baroreflex of Long Evans rats at a site(s) within the brain. Brattleboro rats may maintain normal baroreflex function through mechanisms that do not use, and are not modified by, central AVP.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To test the therapeutic efficacy of immunosuppression with cyclosporine upon the aviremic stage of coxsackievirus B3 (CB3) myocarditis, 2-week-old BALB/c mice were inoculated with 3xlO2plaque-forming units of CB3, and the effects of cyclosporine on peripheral, splenic, and myocardial lymphocyte subsets were investigated. Cyclosporine, 25 mg/kg/day, was administered subcutaneously daily on days 10-31 (experiment 1) and days 30-51 (experiment 2). Treated groups were compared with infected controls for each experiment. In experiment 1, the survival rate of the cyclosporine-treated group was low (17/25 vs. 24/25, p<0.05). The severity of myocardial lesions and the distribution of lymphocyte subsets in myocardium and spleen on days 15-18 did not differ between treated and control groups; on the other hand, the percentages of peripheral Thy 1.2+(pan T) and L3T4+(activated helper T) cells on days 15-18 were decreased in the treated group, and those of B, Lyt 1+(helper/inducer T), and Lyt 2+(suppressor/cytotoxic T) subsets did not differ significantly. Notably, myocardial interleukin-2 receptor (IL-2R) positive cells, through which cyclosporine is considered to act, were scarce in both groups. In experiment 2, survival rates of two groups did not differ (treated, 32/34; untreated, 34/34; /p=NS). The severity of myocardial lesions and the distribution of splenic lymphocyte subsets on days 35-38 also were not different between two groups. The percentages of peripheral lymphocyte subsets (Thy 1.2+and L3T4+were decreased in the treated group; those of B, Lyt 1+, and Lyt 2+subsets did not differ significantly. In experiments 1 and 2, the thymus/body weight ratio in the treated groups was smaller than in the untreated group, but the spleen/body weight ratio in the treated group did not differ from the untreated group; histologically, medullary cellular depletion was evident in the thymus, not in the spleen, of the treated groups. We conclude that cyclosporine failed to change the distribution of lymphocyte subsets in the spleen as well as in the myocardium in CB3 myocarditis although it had effects on the peripheral blood and thymus, which may account for the higher mortality in the treated groups. The absence of beneficial effects of cyclosporine upon the CB3 -infected myocardium may be related to the paucity of cyclosporine-sensitive cells (IL-2R, L3T4, and Lyt 2 positive cells) in the myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To test the hypothesis that during cardiopulmonary resuscitation, chest compression with an unobstructed trachea raises and maintains intrathoracic pressure by collapsing airways and trapping air in the lung, we studied 11 dogs (20-32 kg). An inflatable vest compressed the thorax after induction of ventricular fibrillation. First, tracheal airflow was measured by a pneumotachometer during vest inflation and deflation in nine of the dogs. As expected, during the initial phase of vest inflation of cycles after ventilation, air moved out of the lungs, but then airflow stopped. After vest deflation, however, more air moved out of the lungs in eight of the nine dogs; this occurrence indicated that a portion of the inspired tidal volume was trapped during vest inflation. During cycles without prior ventilation, the amount of air expired by chest compression decreased, paradoxically, at higher peak vest pressures (p<0.002); this occurrence indicated that air was trapped at the higher vest pressures. The change in right atrial pressure was higher on cycles after ventilation than on cycles without prior ventilation (79 ± 12 vs. 67 ± 12 mm Hg [mean ± SEM],p<0.005), and lung volume was higher on cycles after ventilation (p<0.001). Next, a 5-Fr micromanometer was advanced down the airway in eight of the dogs. With the tip of the micromanometer 5-8 cm distal to the carina, a zone of high pressure was noted in seven dogs; this high pressure suggested a zone of airway collapse distal to the carina. With the micromanometer in the high-pressure zone, there was a correlation between the change in airway pressure and the change in right atrial pressure (r=0.90,p<0.001). Finally, contrast was instilled in the airways of four dogs. In all four dogs, collapse of 3-6-mm airways could be visualized during cineradiography. We conclude that air trapping occurs during vest inflation and that this phenomenon explains how intrathoracic pressure can be generated and maintained despite an unobstructed trachea.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID