ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The distribution of tubulin and desmin, the constituent proteins of microtubules and intermediate filaments, respectively, were studied in normal and hypertrophied rat myocardium by high-resolution immunofluorescence and immunoelectron microscopy. Cardiac hypertrophy was induced in 25-day-old rats by aortic stenosis. In the normal heart, double immunolabelling of ultrathin frozen sections of papillary muscle using gold-labelled probes for tubulin and desmin showed that microtubules ran primarily in a longitudinal direction through the intermyofibrillar spaces, perpendicularly to the desmin filaments. Microtubules were present near nuclei, mitochondria, and plasma membranes, while desmin filaments formed transverse connections between adjacent Z disks. No tubulin was observed near the intercalated disks, which were rich in desmin filaments. In hypertrophied hearts, myocytes exhibited the typical morphological features of developing hypertrophy. While there was little difference in the distribution of the microtubules around mitochondria and at the plasma membrane, considerable increases were seen near the nuclei and along the myofibrils. Desmin labelling was distributed transversely as in the controls; however, sometimes it was longitudinally oriented either in the intermyofibrillar space linking 2 Z disks out of register or along digitations of the intercalated disks connecting neighboring desmosomes. The unique rearrangement of desmin and tubulin filaments in hypertrophied cardiac myocytes emphasizes their distinct role in myocyte organization. We suggest that, during the development of cardiac hypertrophy, desmin filaments are mainly involved in maintaining the myofibrils in register, whereas the degree of assembly of microtubules is correlated with the rate of protein synthesis and with myofibrillogenesis.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Arterial baroreceptors are known to influence airway smooth muscle tone. Thus, increasing carotid sinus pressure from 20 to 200 mm Hg causes reflex tracheal dilation. However, the effects of changing sinus pressure around a normal arterial pressure set-point of 100 mm Hg have not been examined. In anesthetized, artificially ventilated dogs, we distended the vascularly isolated carotid sinuses with a pulsatile pressure and recorded isometric tension in an upper tracheal segment. The aortic nerves were cut. Increasing mean carotid sinus pressure in steps between 100 and 200 mm Hg decreased tracheal tension, heart rate, and arterial blood pressure; decreasing sinus pressure between 100 and 25 mm Hg had the opposite effect. Changing carotid sinus pressure still evoked tracheal responses when systemic arterial pressure was held constant. Increasing and decreasing carotid sinus pulse pressure around a constant mean pressure evoked similar changes in tracheal tension. All reflex effects were abolished by cutting or cooling (0°C) the carotid sinus nerves; tracheal responses were abolished by cutting the laryngeal nerves or administering atropine. When carotid sinus pressure was held at 100 mm Hg, cooling the sinus nerves increased tracheal tension. Changes in tracheal tension evoked by the carotid baroreflex were of comparable magnitude to those triggered by stimulating pulmonary stretch receptors, laryngeal receptors, and pulmonary C-fibers. Our results indicate that carotid sinus baroreceptors exert a tonic influence on the upper airways by a vagal cholinergic pathway, increasing and decreasing tracheal smooth muscle tension as blood pressure varies around the normal set-point.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

This study presents a quantitative comparison of the free cytoplasmic calcium concentration ([Ca2+]cyt) and the free concentration in the lumen of the dense tubules of the human platelet. The former was measured by the fluorescence of the high affinity indicator quin2 and latter by the fluorescence of chlorotetracycline (CTC). The CTC technique monitors calcium-CTC complex accumulation in the lumen of dense tubules and mitochondria when washed platelets were incubated in 2 mM Ca2+. Resting cytoplasmic and dense tubular Ca2+concentrations were studied in platelets from patients suffering from venous and arterial thrombosis. Compared with normal controls (0.40 ± 0.10, n = 54), the values of the calcium-CTC ratios were 0.68 ± 0.19 (n = 16, p< 0.005) in venous thrombosis; 0.75 ± 0.18 (N = 14, p< 0.005) in cardiovascular accident; 0.84 ± 0.18 (n = 6, p< 0.005) in occlu-sive peripheral vascular diseases; and 0.42 ± 0.10 (n = 21, p>0.1) in patient controls. The dense tubular Ca2+levels for both patients and controls were perfectly correlated with the cytoplasmic levels using an equation that assumes that the dense tubular free calcium concentration ([Ca2+]dt) has a second power dependence on [Ca2+]cytvl. The abnormal Ca2+handling of platelets obtained from thrombotic patients could be completely reversed by preincubation with the calcium channel blocker verapamil. These observations suggest that the primary Ca2+handling defect is the leakage through activated channels in the plasma membrane. The defect and the elevated resting [Ca2+]cytand [Ca2+]dtare adequate to explain the observation of increased rates of collagen-activated aggregation in the above-mentioned group of patients. The results can be explained by platelets from thrombosis patients being exposed to activating factors in the circulation, resulting in Ca2+channel activation. Channel activation persists through the process of platelet isolation and washing and is manifested in higher measured values of [Ca2+]cytand [Ca2+]dtin the “resting state.” This would bring the platelet closer to its aggregation when aggregation-inducing agents are added. The CTC test is shown to be a useful and convenient means of detecting this abnormality.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The action of procaine on pharmaco-mechanical coupling activated by application of acetylcholine (ACh) was investigated using collagenase-treated dispersed intact and skinned smooth muscle cells and intact muscle tissues of the porcine coronary artery. ACh reduced stored45Ca2+, and this action was prevented by procaine in intact dispersed cells. The maximum reduction in the level of stored45Ca induced by caffeine (25 mM) or inositol 1,4,5-trisphosphate (InsP,; 3 μM) was also prevented by procaine in the skinned muscle cells in the presence or absence of ATP. However, inhibitions of the latter required higher concentrations of procaine than the former. Release by 10 μM ACh of Ca2+from its store site in the presence or absence of extracellular Ca2+was also inhibited by procaine and was detected using the quin2 fluorescence method. In these smooth muscle tissues, ACh (above 10 nM) reduced the amount of phosphatidylinositol 4,5-bisphosphate (PI-P2) and dose dependently increased the amount of phosphatidic acid. Procaine inhibited the hydrolysis of PI-P2activated by ACh, thus reducing the amount of InsP3and the release of Ca2+from the store site. It is concluded that procaine has multiple actions on the porcine coronary artery, and one of the actions related with pharmaco-mechanical coupling appears through inhibition of hydrolysis of PI-P2induced by ACh.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Aortic smooth muscle isolated from spontaneously hypertensive rats (SHR) and normotensive, age-matched Wistar Kyoto rats (WKY) was precontracted by potassium chloride. The relaxant effect of nifedipine (NIF) was much more pronounced in SHR than in WKY, while the relaxation produced by nitroglycerin (NTG) was similar in both tissues. EC50s were (in - log | M |) NIF: SHR 13.1 ± 0.4 and WKY 9.4 ± 0.2 (p<0.05); NTG: SHR 7.35 ± 0.3 and WKY 7.26 ± 0.18 (NS). Aortas from SHR were less sensitive to the contractile effect of Ca2+than their WKY controls (EC50was 3.18 ± 0.03 in WKY and 2.76 ± 0.13 in SHR, p<0.05). The relaxant effect of NIF was dissociated from its effect on Ca2+influx in SHR aortas. NIF 10−10M relaxed the muscle by 100% without producing Ca2+influx blockage, and NIF 10−9and 10−8M induced Ca2+influx blockage while the muscle continued in the relaxed state. Chemically skinned aortic fibers from SHR were less sensitive to the contractile effect of Ca2+than their normotensive (NR) controls (pCa for EC50was 5.91 ± 0.05 in SHR and 6.20 ± 0.03 in NR, p<0.05). NIF 10−1° M depressed the contractile response to Ca2+significantly more in SHR than in NR skinned fibers (pCa for EC50for 5.62 ± 0.09 in SHR and 6.07 ± 0.07 in NR, p<0.05). These data suggest that 1) the more pronounced relaxant action of NIF on SHR aortas cannot be explained by its effect on Ca2+influx, since both effects were dissociated in these vessels; and 2) the mechanism for NIF-dependent relaxation in SHR appears to be located not at the sarcolemmal but at some intracellu-lar level. In this respect, a reduced calmodulin content in SHR arteries, along with an anticalmodulin action of NIF, could explain both the lesser sensitivity to Ca2+and the greater sensitivity to NIF that was found in SHR aortas.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Using the isolated perfused rat heart with transient (10-minute) regional ischemia induced by coronary artery ligation, we have shown that PBN (N-tert-butyl-α-phenylnitrone), an organic spin trap agent designed specifically to form “stable” adducts with free radicals in electron spin resonance studies, can dramatically reduce the vulnerability of the myocardium to reperfusion-induced ventricular fibrillation. Studied in the concentration range of 5-1,000 μM/L, PBN added to the perfusate 5 minutes prior to ischemia exerted a dose-dependent protective effect. At the optimum concentration of 30 μM/L PBN reduced the incidence of ventricular fibrillation to 50% (6 of 12) from its control value of 100% (12 of 12). The antiarrhythmic effect was achieved without any substantial effect on coronary flow or heart rate. Investigating whether this was a direct antiarrhythmic effect, operating during reperfusion, or an indirect effect arising from the action of PBN on the heart during ischemia, PBN (30 μM/L) was added to the perfusion fluid 2 minutes before reperfusion. In the control group, 100% of the hearts fibrillated whereas only 50% fibrillated in the PBN group. Additional studies were designed to ascertain whether the drug caused an absolute reduction in vulnerability to reperfusion-induced arrhythmias (irrespective of the duration of ischemia) or whether it only shifted the ischemic time-reperfusion vulnerability curve to the right (i.e., delayed the onset of vulnerability). Thus, studies were undertaken to define the relation between the duration of ischemia and the incidence of reperfusion-induced arrhythmias in control hearts and hearts treated with PBN. Hearts (12 for each group) were subjected to 5, 10, 20, 30, or 40 minutes ischemia; PBN (30 μM/L) was added to the perfusate either 5 minutes before ischemia or 2 minutes before reperfusion. The results were compared to PBN-free control hearts. In each instance, a bell-shaped time-response profile was obtained. In the PBN-free controls, this gave a maximal vulnerability to reperfusion-induced arrhythmias after 10 minutes of ischemia; in the PBN-treated hearts, this curve was shifted to the right and slightly downwards. These results indicate that the primary action of PBN is to exert a delaying effect, which essentially extends the duration of ischemia that can be tolerated before the heart becomes highly vulnerable to reperfusion-induced arrhythmias. However, this effect is achieved during the reperfusion period and not during the preceding period of ischemia. The precise mechanism by which this free radical spin trapping agent achieves this unusual protective effect remains to be resolved.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The total ATPase activity of myosin and the values for the isozyme V, have been measured in hearts from rats of different ages and with different levels of thyroid function. The contribution of V3was calculated from the difference between total and V1ATPase, neglecting the small contribution of V2. Hearts were quickly frozen after rapid removal from the animals in order to preserve the state of ATPase activity that existed in the intact animal, and ATPase activity was measured in thin sections of tissue by a microphotometric technique. In euthyroid hearts, although cAMP increases total myosin ATPase activity and the activity of V1, the cyclic nucleotide inhibits the ATPase activity of V,. In hearts from rats with developing hypothyroidism following thyroidectomy, the same occurs. After a sufficient period has elapsed after thyroidectomy for V1to have practically disappeared, cAMP has no effect on ATPase activity, but the injection of thyroid hormone restores the effect. Total myosin ATPase activity is maintained relatively constant as the animal ages from 80 to 165 days and during the first 10–11 days following thyroidectomy even though the concentration of V1is dropping. The explanation proposed for these observations is that myosin can exist in two different forms, only one of which can participate in the active generation of force. The transition between the two forms is regulated by a soluble factor that is itself controlled by the adrenergic system. The factor(s) involved in this regulatory mechanism is soluble and can be transferred between different thin sections cut from a frozen heart.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Calcitonin gene-related peptide (CGRP) is present in sensory nerve fibers in the heart and around peripheral arteries. On interaction with specific CGRP binding sites and activation of adenylate cyclase, CGRP causes vasodilation and has positive inotropic and chronotropic effects on the heart. In the present study, human CGRP I and II exerted positive inotropic effects on isolated human right auricles and relaxed small arteries from human skeletal muscle precontracted with norepinephrine (ECS0 for CGRP 10.59 nM and for CGRP II 0.37 nM). CGRP I and II (3.2 nmol) administered i.v. to 6 normal subjects exerted positive inotropic actions on the human heart concomitant with positive chronotropic effects, hypotension, and vasodilation. CGRP may, therefore, be of importance for cardiovascular control in man.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The factors responsible for collateral arterial growth after major artery occlusion remain obscure, despite their importance for tissue survival. An increase in endothelial cell labelling with tritiated thymidine, as an index of collateral arterial growth, occurs early after renal artery occlusion. Our working premise was that an increase in endothelial cell labelling would occur simultaneously throughout the length of the collateral arteries if biophysical factors related to blood flow were the responsible mechanism, because blood flow must be increased simultaneously throughout the length of the small, preformed collateral arterial vessels. On the other hand, if the information spread from the ischemic zone, one would anticipate centripetal spread of the endothelial cell hyperplasia in a retrograde direction from the ischemic zone. With the periureteric collateral arterial supply as the model, we performed serial studies of tritiated thymidine labelling following renal artery stenosis in the rat. As anticipated, endothelial cell labelling rose sharply within 24 to 48 hours, first evident in the area immediately adjacent to the renal hilum. Thereafter, a progressive, time-related centripetal gradient in endothelial cell tritiated thymidine labelling occurred (p <0.01). These findings indicate that the factors responsible for endothelial cell hyperplasia are less related to blood flow in the lumen than to downstream, ischemic events. Although the mechanism responsible for the centripetal spread remains speculative, the communication system is likely to involve cell-to-cell contact in the vessel wall.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID