摘要:

Although multiple forms of myosin in cardiac and skeletal muscles have been identified, it has not been firmly established that myosin isozymes are present in adult smooth muscle. Myosin, extracted from human thoracic aorta and lower saphenous vein and rabbit aorta and uterus, was analyzed by pyrophosphate gel electrophoresis to determine if myosin isozymes are present in these tissues. In all smooth muscle tissues studied, two myosin isozymes were detected and labelled as smooth muscle 1 and smooth muscle 2, smooth muscle 2 being the faster migrating isozyme. Bovine cultured smooth muscle cells from the media of thoracic aorta also contained two forms of myosin. However, cultured fibroblasts contained only one form of myosin. Extracting myosin from either relaxed or contracting rabbit aortic smooth muscle did not influence the mobilities of smooth muscle 1 and smooth muscle 2 on pyrophosphate gels, suggesting that the degree of light chain phosphorylation did not significantly alter the electrophoretic mobility under our conditions. Smooth muscle 1 and smooth muscle 2 myosins each contain heavy chains (200,000 daltons) and light chains (20,000 and 17,000 daltons) in addition to filamin (235,000 daltons), which is closely associated with the native protein. Myosin peptide maps of rabbit aorta and uterus revealed areas of substantially different banding patterns between smooth muscle 1 and smooth muscle 2 from the same tissue. Similar peptide maps of smooth muscle 1 bands were produced from the different tissues, but the smooth muscle 2 maps were dissimilar. Since the speed of shortening of striated muscle appears to be influenced by the myosin isozyme patterns, the possibility exists that the contractile properties of various smooth muscle may also be influenced by the relative amounts of myosin isozymes present.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

In order to test the hypothesis that the increase of vascular resistance observedin vivoat low flow rates is due in part to blood Theological properties, the apparent viscosity of human blood was measured in small tubes in a range of shear rates. Pressure-flow relationships were obtained in vertical glass tubes (29 to 94 μmi.d.) perfused with blood at hematocrits between 0.13 and 0.65. Viscosity of blood and plasma was calculated using Poiseuille's law. With the exception of data obtained in the largest tube at a hematocrit of 0.6, relative blood viscosity was found to be independent of shear rate in the range between 1 and 120 s−1. Microscopic observation revealed pronounced red cell aggregation at low shear rates. Velocity profiles obtained by the use of fluorescence-labelled red cells showed increased blunting with decreasing shear rate. The Fahraeus-Lindqvist effect was evident in a reduction of viscosity with tube size at a given feed hematocrit. The observed constancy of apparent blood viscosity with decreasing shear is attributed to the opposing effects of a cell-depleted marginal layer and red cell aggregation or deformation in the cell core. The findings indicate that the increase of vascular resistance at low arterial pressure cannot be explained by shear-dependent changes of apparent blood viscosity observed in macroviscometers.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

To determine if mature coronary collateral vascular smooth muscle contains functioning α-adrenergic receptors, we studied 13 dogs, 6–10 months after circumflex ameroid occlusion. Regional myocardial blood flow was measured with radioactive microspheres in a blood-perfused heart preparation at constant aortic pressure (80 mm Hg). Normal zone resistance was calculated as aortic pressure divided by normal zone flow, and transcollateral resistance was calculated as aortic pressure minus circumflex pressure distal to the ameroid constrictor divided by coronary collateral flow. Flow and resistance were measured during adenosine vasodilation before and during graded doses of a constant infusion of the α-adrenergic agonist methoxamine (n= 6) or the α2-adrenergic agonist clonidine (n= 7). In the hearts that received methoxamine, normal zone resistance increased from a control of 0.29 ± 0.06 to 0.39 ± 0.06 mm Hg × min/ml per 100 g (resistance units) during infusion of 10-!M methoxamine (p < 0.05). In contrast transcol lateral resistance averaged 0.24 ± 0.02 resistance units under control conditions and did not change during methoxamine infusion. In the hearts that received clonidine, normal zone resistance averaged 0.24 ± 0.03 resistance units and increased to 0.39 ± 0.07 resistance units (p< 0.05) with the highest dose of clonidine administered (10−5M). Transcollateral resistance averaged 0.17 ± 0.03 resistance units during control conditions and did not change with clonidine infusion. In separate studies isometric tension development by the left anterior descending and coronary collateral vessels was examined in organ baths. The left anterior descending coronary artery demonstrated dose-dependent constriction to phenylephrine (peak response 22 ± 5% of the response to 100 mM KCI). Clonidine produced weak constrictor responses in the left anterior descending coronary artery (5 ± 2.5% maximal KCI response). In contrast, neither phenylephrine nor clonidine produced responses in mature collaterals. We also examined responses of mature collateral vessels to nonadrenergic agonists. In the vascular ring preparation the mature collaterals developed tension in the presence of KCI (2.3 ± 0.9 g), prostaglandin F2α(16 ± 8% of the KCI responses), and vasopressin (90 ± 30% of the KCI response). In adenosine-vasodilated hearts, pharmacologic doses of vasopressin caused a two-fold increase in transcollateral resistance. Thus, these studies performed on intact hearts and isolated vascular rings demonstrate that mature coronary collaterals do not contain functioning α-adrenergic receptors. Consequently, mature coronary collateral resistance is not regulated by α-adrenergic neurohumoral mechanisms.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The dissociation of adult rat heart into individual, functionally intact, calcium-tolerant myocytes requires precise manipulation of extracellular calcium levels. Dissociation of intercellular connections is achieved by lowering extracellular calcium to micromolar levels for a short period. By imposing a very small increment in free calcium activity (from 14 to 17 μM)during this period, we achieve a significant yield of functionally intact pairs of myocytes still joined at the intercalated disc. We obtain fewer intact cells, but many of these are paired end to end. These findings permit us to describe some structural characteristics of intercellular connections between cardiac cells and to report unambiguous measurements of electrotonic coupling and dye transfer between rat cardiac cell pairs. We find that the strength of electrical coupling between cells isolated as pairs with intact junctional contacts is much greater than that measured between cell pairs that have formed new junctional contacts.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of milrinone were studied in ferret papillary muscle stimulated at various rates and temperatures from 23° to 36° C. In voltage-clamp experiments, 50 μg/ml (0.237 mM) milrinone induced a 2.1-fold increase in calcium current at 28° or 36°C. At 50 μg/ml, milrinone transiently increased contractility in all muscles at 28°C, but its steady-state effect was either increased (+ 50%) or decreased (−24.7%) steady-state twitch amplitude. A negative inotropic effect always occurred below 27° C. Milrinone decreased the total twitch duration and split the twitch into two components (P1 and P2) in the absence of any evidence of aberrant conduction. Increasing milrinone concentration from 50 to 300 μg/ml decreased P1 and increased P2. Ryanodine (100 mM) or caffeine (10 mM) suppressed P1. Contractions elicited after 30 seconds of rest were also biphasic in the presence of milrinone, but not in its absence. P2 of post-rest contraction was increased by caffeine or calcium (10 mM) and decreased by cobalt (2 mM) when drugs were applied at the beginning of the rest. Ryanodine and caffeine also suppressed P1 of post-rest contraction. The evidence suggests that P1 may be caused by Ca release from the sarcoplasmic reticulum and P2 by increased Ca influx during the action potential via the calcium channel. It is also suggested that P2 may be present under control conditions, but to a lesser extent, and masked by a large P1.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effect of adenosine on the vascular density of the chick chorioallantoic membrane was studied. Elvax polymer pellets containing 0.2–3.0 mg of adenosine were placed on the chorioallantoic membrane of 10-day embryos. Control pellets containing mannitol were placed at least 1 cm away. After 4 days the membrane was formalin-fixed and removed. A thin plastic coverslip, inscribed with concentric circles (4–8 mm in diameter), was placed over the pellet. A vascular density index was estimated at 20x by counting the number of intercepts between vessels and the inscribed circles. Adenosine stimulated a dose-dependent increase (p<0.01) in the vascular density index with the 3-mg pellets inducing a 15% increase. Inosine, a major metabolite of adenosine, did not cause a change in the number of intercepts counted. The adenosine-stimulated increase in vascularity was blocked with 110 μg of methyl-isobutyl-xanthine injected daily into the albumin. Partial inhibition was observed with 55 μg/day. Methyl-isobutyl-xanthine by itself did not affect the vascular density index. Dipyridamole enhanced adenosine's stimulation of vascular growth an additional 52%. Given alone, however, it had no effect on the membrane's vascularity. These data support an angiogenic role for adenosine. The modest, but consistent, increase in the vascular density index stimulated by adenosine, and the fact that it may be released during tissue hypoxia, is consistent with an hypothesis that this nucleoside plays a modulatory role in vessel proliferation accompanying conditions of long-term hypoxia.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The clonal smooth muscle cell line A10, derived from fetal rat aorta, binds125I-lnsulin-like growth factor I at a Type 1 insulin-like growth factor receptor. Threonine-59 insulin-like growth factor I, multiplication stimulating activity, and insulin inhibit the binding with IC50= 10 nM, 84 nM, and 500 nM, respectively. Insulin in high concentrations (>5 μM) completely inhibits125I-insulin-like growth factor I binding to A10 cells. Threonine-59 insulin-like growth factor I and insulin stimulate [3H]thymidine incorporation into DNA in A10 cells that had been growth arrested by incubation in serum-free media (DMEM/0.1% BSA) for 24–36 hours. The stimulation produced by the peptides is 50–60% of the stimulation produced by 10% fetal calf serum. Low levels of serum (0.1 and 0.5%) also stimulate DNA synthesis, and the effects of Threonine-59 insulin-like growth factor I and low serum are additive. The ED50for the effects of Threonine-59 insulin-like growth factor I, multiplication stimulating activity, and insulin are 6.8 % 0.3 nM, 36 % 2.5 nM, and 360 % 242 nM, respectively. Incubation of A10 cells for 24 hours with Threonine-59 insulin-like growth factor I or serum increases the protein content per culture dish by 85 % 21 and 183 % 26%, respectively (mean % SEM). Thus, both protein levels and DNA synthesis are increased by incubation with peptides. However, Threonine-59 insulinlike growth factor I does not increase the number of cells in serum starved cultures, although 10% fetal calf serum does. Platelet-derived growth factor also stimulates DNA synthesis in A10 cells, but epidermal growth factor and acidic fibroblast growth factor do not. The effects of platelet-derived growth factor and Threonine-59 insulin-like growth factor I are additive. DNA synthesis begins 12 hours after the addition of Threonine-59 insulin-like growth factor I or serum to growth-arrested A10 cells. Threonine-59 insulin-like growth factor I can be removed from the cells after 8 hours, and maximal stimulation of DNA synthesis still occurs. Thus, a minimum 8-hour exposure of A10 cells to Threonine-59 insulin-like growth factor I is necessary to initiate the events required for the cells to progress from G1 to S phase. These data suggest that insulin-like growth factor I stimulates DNA synthesis in the A10 rat vascular smooth muscle cell line in the absence of serum and other exogenously added growth factors. However, insulin-like growth factor I alone apparently is not sufficient for cells to progress from S phase to cell division.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

In 57 normal subjects (age 20–60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90° upright tilt, controlled respiration (n = 16) and acute(n =10) and chronic(n =12) β-adrenergic receptor blockade. Automatic computer analysis provided the autoregressive power spectral density, as well as the number and relative power of the individual components. The power spectral density of R-R interval variability contained two major components in power, a high frequency at ∼0.25 Hz and a low frequency at ∼0.1 Hz, with a normalized low frequency: high frequency ratio of 3.6 ± 0.7. With tilt, the low-frequency component became largely predominant (90 ± 1%) withalow frequency: high frequency ratio of 21 ± 4. Acute β-adrenergic receptor blockade (0.2 mg/kg IV propranolol) increased variance at rest and markedly blunted the increase in low frequency and low frequency: high frequency ratio induced by tilt. Chronic β-adrenergic receptor blockade (0.6 mg/kg p.o. propranolol, t.i.d.), in addition, reduced low frequency and increased high frequency at rest, while limiting the low frequency: high frequency ratio increase produced by tilt. Controlled respiration produced at rest a marked increase in the high-frequency component, with a reduction of the low-frequency component and of the low frequency: high frequency ratio (0.7 ± 0.1); during tilt, the increase in the low frequency: high frequency ratio (8.3 ± 1.6) was significantly smaller. In seven additional subjects in whom direct high-fidelity arterial pressure was recorded, simultaneous R-R interval and arterial pressure variabilities were examined at rest and during tilt. Also, the power spectral density of arterial pressure variability contained two major components, with a relative low frequency: high frequency ratio at rest of 2.8 ± 0.7, which became 17 ± 5 with tilt. These power spectral density components were numerically similar to those observed in R-R variability. Thus, invasive and noninvasive studies provided similar results. More direct information on the role of cardiac sympathetic nerves on R-R and arterial pressure variabilities was derived from a group of experiments in conscious dogs before and after bilateral stellectomy. Under control conditions, high frequency was predominant and low frequency was very small or absent, owing to a predominant vagal tone. During a 9% decrease in arterial pressure obtained with IV nitroglycerin, there was a marked increase in low frequency, as a result of reflex sympathetic activation. Bilateral stellectomy prevented this low-frequency increase in R-R but not in arterial pressure autospectra, indicating that sympathetic nerves to the heart are instrumental in the genesis of low-frequency oscillations in R-R interval.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Effects of thyroid hormone on α-actin and myosin heavy chain gene expression were compared in ventricle, soleus, and extensor digitorum longus muscles of hypothyroid rats. Changes in mRNA content were analyzed using synthetic oligonucleotide probes complementary to the unique 3′ untranslated regions of four striated myosin heavy chain mRNAs and cardiac and skeletal muscle α-actin mRNAs. The results indicate that daily treatment with 3,5,3′-triiodo-L-thyronine (2 μg/100 g body weight) increased α-myosin heavy chain mRNA content in heart muscle by 500% and decreased β-myosin heavy chain mRNA by 65% within 48 hours. β-mRNA in extensor digitorum longus was decreased by 60% at 48 hours while in soleus, β-mRNA levels were not affected by 9 weeks of treatment. Fast Ha mRNA was present in small amounts in hypothyroid soleus and increased by 150% and 200% after 7 and 9 weeks of thyroid hormone administration, respectively. Fast lib mRNA also was found in hypothyroid soleus and a small increase (60%) was observed after 1 day of treatment. In extensor digitorum longus, Fast IIb mRNA increased by 200% and Fast IIa mRNA decreased by 50% after 1 week of treatment. When larger daily doses of thyroid hormone (15 μg/100 g body weight) were administered, similar changes in mRNA levels were observed, except that β-mRNA content of soleus muscle was decreased slightly (25%). Expression of the cardiac form of α-actin was induced transiently in ventricle, but the skeletal form of α-actin mRNA in soleus and extensor digitorum longus did not change significantly after thyroid hormone treatment. Skeletal α-actin mRNA was not found in ventricle, and cardiac α-actin mRNA was not detected In skeletal muscles. Thus, cardiac α-actin mRNA levels are transiently stimulated in ventricle by thyroid hormone treatment while all of the myosin heavy chain genes expressed in adult striated muscles are affected in a complex, tissue-specific manner.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Experiments were designed to separate effects of myocardial oxygen tension and oxygen consumption on coronary autoregulation. The approach was to measure coronary hemodynamic and metabolic responses to decreases in perfusion pressure during interventions that altered the balance between myocardial oxygen supply and demand. Studies were conducted in anesthetized heart-blocked dogs with the left coronary artery perfused from a pressure-controlled blood reservoir. Decreasing oxygen consumption by lowering heart rate from 120 to 40 bpm increased coronary venous oxygen tension and reduced the degree of flow autoregulation between 120 and 80 mm Hg by threefold. In contrast to effects of bradycardia, coronary constriction with vasopressin or indomethacin (heart rate 120 bpm), which produced comparable increases in baseline vascular resistance, decreased coronary venous oxygen tension, and augmented flow autoregulation by nearly twofold. Initial coronary venous oxygen tension but not oxygen consumption was strongly correlated with a quantitative index of autoregulation (−0.052 Po2+ 2.01, R2= 0.86) over the pressure range of 120 to 80 mm Hg. When heart rate was lowered to 40 bpm and coronary venous oxygen tension subsequently reduced with vasopressin to control values (120 bpm), autoregulation was completely restored. Parallel studies examined the effects of metabolic and pharmacologic interventions on coronary pressure-flow relations over a wide range of pressures. For each 20 mm Hg decrement in pressure between 160 and 80 mm Hg, lowering heart rate attenuated autoregulation whereas pharmacologic coronary constriction augmented autoregulation. The observed variations in the autoregulation index were largely explained by differences in the prevailing venous oxygen tension. Furthermore, the upper pressure limit for autoregulation was dependent on venous oxygen tension with a threshold oxygen tension for autoregulation of 32 mm Hg. These results indicate that coronary autoregulation is closely coupled to the prevailing venous oxygen tension but not oxygen consumption and is facilitated at low venous oxygen tension.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID