摘要:

We studied the effects of factors that alter active Na extrusion on microvascular smooth muscle contraction. As an index of contraction, we measured arterial pressure in perfused isolated rat hindlimbs. The perfusate was oxygenated Krebs-Henseleit solution containing 0-5.9 mM K+, 4% dextran-40, and, in some instances, dog red cells (6-15% hematocrit). The reference solutions contained 5.9 mM K+. Lowering [K+]oby 50%, or more, substantially increased perfusion pressure reversibly; pressure was inversely related to [K+]o. Treatment with 10"3M ouabain, which should completely inhibit Na-K pumps, caused a greater pressure increase than did nominally K+-free media. These effects were observed in the hindumbs of reserpine-treated (catecholamine-depleted) as well as normal rats and, thus, cannot be explained by modulation of catecholamine release. Perfusion with solutions containing a constant concentration of norepinephrine increased the perfusion pressure with 5.9 HIM K present and augmented the responses to both reduced [K+]oand ouabain. The data are discussed in terms of two mechanisms that may lead to a rise in cell Ca2+: (1) inhibition of electrogenic Na-K pumps may cause the smooth muscle fibers to depolarize slightly, thereby activating a Ca2+conductance increase or release of stored Ca2+, and/or (2) the rise in cell Na*, due to Na-K pump inhibition, may cause the fibers to gain Ca2+by means of Na-Ca exchange.Circ Res 46: 463-470, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Although the ultrasonic pulsatility index (PI) is used as a test of arterial inflow, the relationship between proximal arterial stenosis and PI has not been fully evaluated. In a series of experiments on dogs, over 200 measurements of pressure, flow (using an indwelling electromagnetic flowmeter), and PI were made distal to implanted arterial stenoses of varying length (0.5-9 mm) and cross-sectional area (36-94% reduction in area). It was shown that, whereas the reduction of PI correlates broadly with stenosis severity, the scatter of results is wide for all but the tightest stenoses. This scatter is due at least in part to the variability of the vascular bed distal to the site of measurement. Circ Res 46: 470-475, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Bradykinin applied directly to the epicardium evokes a reflex increase in blood pressure by stimulating sympathetic afferent nerve endings in the heart, but injected into the coronary artery it evokes vagally mediated reflex decreases in heart rate and blood pressure. The afferents initiating these latter depressor effects have not been identified. We have attempted to determine which vagal sensory nerve endings in the heart are stimulated by bradykinin. In anesthetized dogs, we recorded impulses from afferent vagal fibers with endings in the heart and aorta and injected bradykinin (0.3-1.0 /ig/kg) into the left atrium. Neither Anor C-fiber mechanoreceptors nor aortic body chemoreceptors were stimulated directly by bradykinin, any changes in firing of a trial or ventricular mechanoreceptors, or of aortic baroreceptors or chemoreceptors, being secondary to the cardiovascular effects of bradykinin. However, 16 of 20 irregularly discharging vagal C-fibers with chemosensitive endings in the left ventricle, left atrium, and aorta were stimulated by bradykinin; firing increased from 0.2 ± 0.1 to 7.8 ± 1.4 (mean ± SE) impulses/sec and usually remained above control for about 30 seconds. These chemosensitive endings were not stimulated by ventilating the lungs with 5% O2in N2, but they were stimulated by injecting capsaicin or phenyl diguanide into the left atrium. Four chemosensitive endings in the ventricular epicardium were also stimulated by dripping bradykinin (1 pg/ml) onto the heart. We suggest that these chemosensitive vagal C-fibers are responsible for the reflex decreases in heart rate and blood pressure elicited by bradykinin.Circ Res 46: 476-484, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Myocardial ischemia alters the immunofluorescent staining pattern of lysosomal cathepsin D from one that is essentially participate to one in which a diffuse staining pattern predominates. Prolonged starvation causes an apparently similar redistribution of cathepsin D from discrete secondary lysosomes to diffusely staining sites. However, because of the limits of resolution of immunofluo-rescence techniques, it has not been possible previously to define the exact nature and location of cathepsin D staining in these conditions. Accordingly, a new procedure employing peroxidase-labeled antibodies has been developed to allow localization of cathepsin D with electron microscopy. Most of the cathepsin D that can be detected in normal hearts with this technique is present in classic lysosomal structures, analogous to the particulate staining pattern seen with immunofluorescence microscopy. The technique also reveals, for the first time, definitive ultrastructural evidence that ischemia induces lysosomal leakage and redistribution of cathepsin D into the cytoplasm. Starvation is not accompanied by release of cathepsin D into the cytoplasm; rather, there is widespread, increased distribution of cathepsin D within elements of the sarcoplasmic reticulum, whose diameters are too small for resolution with light microscopy. Thus, although both ischemia and starvation increase nonsedimentable cathepsin D activity, as measured biochemically, and produce a diffuse staining pattern under immunfluorescence microscopy, electron microscopy reveals a distinctly different subcellular distribution for this enzyme in the two conditions. These results emphasize that considerable caution must be exercised in interpreting biochemical and histochemical changes suggestive of enzyme release from lysosomes, in the absence of supportive ultrastructural evidence.Circ Res 46: 485-494, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We reviewed the absolute amd differential growths of the myocyte populations in the left(L) and right (R) ventricular myocardium morphometrically from 1 to 5 days and from 5 to 11 days after birth. From 1 to 11 days hypertrophy of the average myocyte in the ventricles was (L) 2.7- and (R)2.4-fold, and myocyte proliferation was (L) 2.0- and (R) 1.2-fold. Mean cell volume, cell length, and percent binucleation of cardiac myocytes were similar in both ventricles at 1, 5, and 11 days of age. During this period, average myocyte length increased 2-fold (12 sarcomere lengths), and the percentage of binucleate myocytes increased approximately from 2.7 to 17 to 48%. Myocyte hypertrophy from 1 to 5 days resulted mainly from an increase in the volume of cytoplasm per nucleus and from 5 to 11 days from the accumulation of binucleate cells. No differences were observed in the characteristics of epicardial and endocardial myocytes in either ventricle up to 11 days of age. The 61% greater proliferation of myocytes in the left ventricle was the principal basis for the development of a 2-fold difference in ventricular weight gains: (L) 6.2- and (R) 3.4-fold. No increase in right ventricular midwall thickness was observed, in contrast to a 2.7-fold increase of the left ventricle. It was concluded that, asa result of the circulatory changes occurring shortly after birth, right ventricular growth is analogous to eccentric hypertrophy, whereas left ventricular growth represents a combination of eccentric and concentric hypertrophy.Circ Res 46: 495-502, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

The absolute and differential growths of the capillary network and of myocyte cytoplasmic components in the left (L) and right (R) ventricular free walls were measured morphometrically from 1 to 5 days and from 5 to 11 days after birth. From 1 to 11 days, capillary length, luminal volume, luminal surface area, and endothelial cell volume each increased 2-3 times more rapidly than myocardial mass or myocyte mass in each ventricle. Mean intercapillary distance and the transverse crosssectional area of the average capillary decreased markedly. The mean number of capillaries across the ventricular walls increased from 16 to 79 (L) and 14 to 22 (R). Maturation of the cytoplasm of left and right ventricular myocytes from 1 to 11 days included increases in the volume percentage of myofibrils(1.2-fold), mitochondria (1.8-fold), and smooth endoplasmic reticulum (2.1-fold) and increases in mean mitochondrial size [1.9-fold (L), 1.2-fold (R)] and number per cell [2.7-fold (L), 3.6-fold (R)]. Despite a 2-fold greater overall left ventricular growth, the myocardial compositions of both ventricles were nearly indistinguishable at 1 and 11 days. Both subcellular and microvascular changes, however, were generally achieved more rapidly in the left ventricle from 1 to 5 days of age, demonstrating many structural differences and a lagging development in the right ventricle at 5 days. Thus, postnatal myocardial adaptation to the altered work demands on the left and right ventricles shortly after birth resulted in morphological changes that could be the basis for a transient disparity in ventricular functions at about 5 days of age.Circ Res 46: 503-512, 19S0

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Muscular subaortic stenosis (MSS) is a genetically determined cardiomyopathy, whereas right ventricular infundibular hypertrophy (IH) apparently is an acquired condition. Since genetic expression in eukaryotic cells may be regulated primarily by DNA-associated proteins, we isolated and characterized the proteins of heart nuclei from nine patients with MSS, eight with IH, and two with normal (N) hearts. More than 150 proteins could be identified by two-dimensional polyacrylamide gel electrophoresis. Proteins in the entire region from pH 7.0 to 9.0 with molecular weights (Mr) ranging from 35,000 to 41,000 and a protein focusing from pH 5.2 to 5.3 with Mrof 55,000 were strikingly reduced in MSS. Again the electrophoretic patterns of N and IH were similar. The electrophoretic patterns of nonhistone nuclear protein (NHNP) in MSS relative to N showed a striking resemblance to those demonstrated previously for the early stage (myolytic phase) of hamster cardiomyopathy relative to the matched control. Since NHNP interacting with DNA appears to play a major role in genetic expression, it is possible that some of the manifestations of MSS could be due to different components of NHNP in the affected hearts.Circ Res 46: 513-519, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We used enzyme digestion to isolate cells from aortas of Rhesus monkeys (Macaca mulatto) fed on control or atherogenic diets for 19-21 months and subjected them to Metrizamide density gradient centrifugation. A majority of the cells from both control and experimental animals equilibrated in the density range of 1.08-1.12, but an additional population of cells (about 10% of the total) equilibrating at lower densities (p = 1.04-1.07) was present in preparations from diseased vessels. Except for a 10-fold increase in esterified cholesterol in cells from diseased aortas, the high density cells of both groups exhibited similar levels of marker enzymes of organelles [iV-acetyl-/?-glucosaminidase and /?-galactosidase (lysosomes), neutral a-glucosidase (endoplasmic reticulum), 5′-nucleotidase (plasma membrane), and catalase (catalase-bearing particles)] and contained similar amounts of unesterified cholesterol. Electron microscopy revealed the high density cells as smooth muscle cells, with many of those from diseased vessels containing cytoplasmic lipid droplets and lipid-containing lysosomes. The latter were identified by acid phosphatase cytochemistry. The low density cells were enriched in both free and esterified cholesterol, acid hydrolases, and catalase. They appeared morphologically as foam cells heavily laden with lipid, which was present as cytoplasmic lipid droplets and as lipid-containing lysosomes. The cytoplasmic lipid droplets occupied 34-38% and the lipid-filled lysosomes another 18-23% of the cytoplasmic volume of the foam cells. The proportion of total aortic cholesterol associated with cells was found to be 22.1 ± 7% (n = 3) in the control aortas and 17.0 ± 4% (n = 4) in the diseased aortas. Circ Res 46: 520-530, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We developed a mathematical model of the right and left ventricles to determine whether there is a change in the mechanical properties of muscle during the hypertrophy process resulting from pulmonary arterial banding. Pressure-volume data were obtained from 10 normal dog hearts and 8 dog hearts in which the pulmonary artery was banded for periods of 2-40 weeks. These data were applied to the model, and the time course of wall stress and muscle stiffness was quantified for both ventricles. The results demonstrate that (1) myocardial stiffness is increased in pressure-overload hypertrophy (2) normal right and left ventricular muscle exhibits similar mechanical properties and(3) the relationships between wall stresses and the volume/mass ratios to the period of banding are biphasic. We concluded that (1) increase in muscle stiffness is due to several factors. In the early stages of hypertrophy, it may be predominantly due to fibrosis and, in the later stages, to substantial increases in muscle mass. (2) The progressive increase in muscle stiffness concomitant with the increase in muscle mass may be due to the presence of myocardial cellular projections and fibrosis. (3) The appropriate timing for surgical/medical intervention should take place before low volume: mass ratios and, hence, low wall stresses are attained. Circ Res 46: 530-542, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Action potentials were recorded from canine Purkinje fibers to evaluate the effects of external calcium and the slow inward current-blocking agents, manganese and verapamil, on the relationship between action potential duration and diastolic interval during both steady state and premature excitation. Elevated external calcium shortened the action potential without changing the dependence of either steady state or premature responses on the preceding diastolic interval. The effects of elevated calcium resembled those of increased stimulation frequencies in that the duration of the steady state action potential was reduced without a concomitant change in the interval dependence of the premature action potentials. In contrast, manganese and verapamil markedly slowed the recovery of the premature action potential duration with increasing diastolic interval, but did not significantly alter the steady state relationship. On the basis of these experiments, we conclude that (1) the mechanisms underlying the immediate and cumulative cycle length-dependent changes in action potential duration are separate processes; (2) the abrupt decrease in action potential duration following a reduction in cycle length is consistent with the incomplete recovery of the plateau currents, whereas the steady state changes involve a slower process, possibly an increase in potassium conductance mediated by an accumulation of internal calcium; and (3) the slower frequency-dependent changes do not depend on calcium entry through the slow inward current channel.Circ Res 46: 543-552, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID