摘要:

&NA;The influence of acute hypoxia (respiration gas 12%, 10%, and 8% O2and asphyxia, respectively) on 1) the density of perfused capillaries and muscle fibers, and 2) the capillary red cell distribution was investigated in the left heart of anesthetized rats. To observe capillaries and fibers, fluorescein isothiocyanate‐labeled (FITC)‐&ggr;‐globulin and lissamine‐rhodamine‐B200‐labeled (RB200) myoglobin were injected intravenously as labels of the perfused intravasal and the extracellular space, respectively. The hypoxic conditions were induced subsequently and maintained for 3 minutes. After this period the heart was rapidly frozen for histological demonstration of the dyes. Ventilation with 12% or 10% O2did not induce any changes in the density of perfused capillaries; however, 8% O2in respiration gas did lead to a significant increase (capillaries/mm2: subepicardium, 4,180, controls, 3,620; subendocardium, 3,930, controls, 3,240). A similar increase was found in the asphyxia group (capillaries/mm2: subepicardium, 4,170; subendocardium, 3,700). The increases in the density of perfused capillaries were paralleled by rises in fiber density. This leads to the conclusion that the changes in capillary counts were caused by fiber elongation with a resultant decrease in intercapillary distances. This assumption was supported by observations that there were no signs of changes in ventricular segment length during respiration of 12% or 10% O2but that an increase did occur with 8% oxygen and with asphyxia. Densities of perfused capillaries exactly coincided with anatomical densities (demonstrated by additional labeling of capillary basement membranes with isolectin B4) in normoxic and asphyctic hearts. The distribution of red cells in the capillaries, determined in histological sections, did not differ appreciably under hypoxia due to reduced O2in respiration air (12%) or asphyxia. The results obtained indicate that 1) extreme hypoxic states cause the capillaries to move closer to each other due to elongation of myocardial fibers and 2) red cell distribution is not altered during these conditions. (Circulation Research1989;64:742‐752)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;To study the effects of myocardial hypertrophy resulting from chronic pressure overload on excitation‐contraction coupling, the cardiac transmembrane L‐type calcium current (ICa) was investigated in the Goldblatt renovascular hypertensive (HBP) rat. ICawas measured in single myocytes enzymatically isolated from control (CTRL) and HBP rat hearts using the whole‐cell, patch‐clamp method. The peak ICaand ICadensity (obtained by normalizing ICato the average cell capacitative surface area) were larger in HBP cells (n=15) than in CTRL cells (n=10) at membrane potentials of −20 to 50 mV (p<0.01). The maximal peak ICaincreased from 0.9±0.5 nA (mean±SD) in CTRL cells to 2.8±1.0 nA in HBP cells (p<0.001). The corresponding ICadensity increased from 5.3±2.7 to 16.2±6.0 &mgr;A/cm2(p<0.001). There was no shift in the current‐voltage relation between CTRL and HBP cells. The time course of decay of HBP ICain response to clamp steps to the plateau range of the action potential (membrane potential, Vm= −10 to 30 mV) was delayed when compared with that of CTRL ICa. The inactivation time constants (biexponential) for the maximal ICawere 6.9±1.9 and 36.0±9.3 msec for CTRL cells and 6.7±1.4 and 49.5±12.9 msec for HBP cells (p<0.05 for the slower component of the maximal ICa). There was no difference in the steady‐state inactivation of ICa(fœ) for the CTRL and HBP cells. From the maximal peak ICa, cytoplasmic free Ca2+was estimated to reach a pCa of 6.95±0.07 for CTRL cells and 6.64±0.13 for HBP cells. It is concluded that ICais increased with myocardial hypertrophy. The lengthening of the action potential in hypertrophied rat myocardium is due to an increase in peak current density and to the slower inactivation of the maximal ICa. The increased transmembrane flux of Ca2+via ICain HBP cells is inadequate to achieve a myoplasmic free Ca2+level sufficient for direct partial activation of the contractile myofilaments. However, in the scheme of the calcium‐triggered calcium release hypothesis such an increase could provide an increased amount of activator calcium and/or serve to amplify the release of Ca2+from sarcoplasmic reticulum, thereby contributing to preserved peak developed tension in hypertrophied rat myocardium. (Circulation Research1989;64:753‐763)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;We studied whether the oxygen cost of mechanical energy is time‐invariant in the excised, cross‐circulated canine heart. The total mechanical energy generated by ventricular contraction can be quantified by the total pressure‐volume area (PVA) according to the time‐varying elastance model. In this model, mechanical energy generated until a specified time (t) during systole can be quantified by the partial pressure‐volume area, PVA(t). PVA(t) was obtained by quickly releasing ventricular volume at a varied time during isovolumic contraction. The quick release aborted further development of mechanical energy. We found that PVA(t) at a constant end‐diastolic volume linearly correlated with myocardial oxygen consumption (Vo2). This indicates that the oxygen cost of mechanical energy is time‐invariant. However, we also found that the slope of the Vo2‐PVA(t) relation decreased with increasing quick‐release speed. This indicates a decrease in Vo2by the quick release despite the same PVA(t). The time‐invariant oxygen cost of mechanical energy is consistent with the time‐varying elastance model of the ventricle, but the decreased Vo2with increasing quick‐release speed despite the same PVA(t) is not. (Circulation Research1989;64:764‐778)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;The cardiac high molecular weight proteins/ryanodine receptors were purified to homogeneity from junctional sarcoplasmic reticulum membranes and shown to exhibit large conductance calcium channel activity. High molecular weight proteins were solubilized from junctional sarcoplasmic reticulum in zwitterionic detergent and purified by size‐exclusion chromatography followed by sucrose density gradient centrifugation. The purified proteins exhibited an apparent Mr= 400,000 ‐ 350,000, and bound [3H]ryanodine with aKdof 4.6 nM and aBmaxof 140‐280 pmol/mg protein. High molecular weight proteins demonstrated divalent cation channel activity after incorporation into planar lipid bilayers. Two channel types were identified. Large conductance channels had a slope conductance of 96±13 pS and a Erevof 42±9 mV (n=5); small conductance channels had a slope conductance of 5.5±1 pS [1.0 &mgr;M cis CaCl2; 50 mM trans Ba(OH)2]. Reducing cis calcium from 1 &mgr;M to 1 nM reduced the large conductance channel open time from 7±1% to 0.1% (holding potential, −100 mV). Adding ATP (1 mM) to the cis chamber increased channel open time from 6±1% to 52±4% (holding potential, −100 mV); 10 nM ryanodine increased and 100 &mgr;M ryanodine decreased percent of open time of the 96 pS channel, without altering unitary channel conductance. The large conductance channel was similar to the calcium release channel detected in native canine cardiac junctional sarcoplasmic reticulum vesicles. Our data suggest that the ryanodine receptor, the calcium‐release channel, and the high molecular weight proteins are all identical proteins containing allosteric regulatory sites for calcium, ATP, and ryanodine. (Circulation Research1989;64:779‐789)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Pressure‐diameter relations were studied in rat afferent arterioles using an isolated, juxtamedullary nephron preparation perfused with a saline solution containing 5% albumin. Angiotensin I (10 &mgr;M), angiotensin II (0.1 &mgr;M), and norepinephrine (10 &mgr;M) increased perfusion pressure, and norepinephrine, but not angiotensin I or II, contracted afferent arterioles, indicating that the vessels are reactive. The control diameter of the afferent arterioles that exhibited pressure‐dependent contraction (n=58) averaged 30.8±1.1 &mgr;m at perfusion pressure of 80 mm Hg. When pressure was increased from 80 to 120 and then to 180 mm Hg, the diameter of these arterioles decreased by 16.4±2.1%. Glomerular capillary pressure was well autoregulated and averaged 45.2±2.2, 50.2±2.4, and 53.0±3.0 mm Hg, respectively, at perfusion pressures of 80, 120, and 180 mm Hg. Administration of vasodilators or a Ca2+‐free solution eliminated the contractile response to pressure elevations; rather, the diameter of these vessels increased significantly by 17.5±5.1% and 32.0±9.4%, respectively, when pressure was increased from 80 to 180 mm Hg. Blocking tubuloglomerular feedback mechanism, with furosemide or by removal of the renal papilla (which interrupts the delivery of fluid to the macula densa), eliminated the pressure‐dependent contraction of the afferent arterioles. Instead the diameter of these vessels increased by 27.0±7.8% and 36.0±5.6%, respectively, when the pressure was increased from 80 to 120 and then to 180 mm Hg. These results demonstrate that juxtamedullary nephrons perfused in vitro autoregulate glomerular capillary pressure. This effect is mediated via a contraction of the terminal portion of afferent arterioles and is dependent on the tubuloglomerular feedback mechanism. (Circulation Research1989;64:790‐798)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Release of atrial natriuretic factor (ANF) following an elevation in heart rate is thought to be mediated primarily by a change in atrial stretch. To evaluate the direct effect of chronotropic stimulation on ANF release, isolated rat left atria were electrically paced (1‐9 Hz) at constant resting tension (0.5‐4 g), and the amount of immunoreactive ANF (IRANF) released at each frequency and tension was quantitated with a sensitive radioimmunoassay. Our results show that at controlled resting tensions greater than 1 g, chronotropic stimulation increased IRANF secretion in a manner dependent on the pacing frequency; rapid atrial rates (e.g., 8 and 9 Hz) were necessary to release ANF at tensions of 1 g or less. Resting tension influenced the magnitude of the secretory response to electrical stimulation. Release of IRANF with contraction frequency was transient in nature and, at high frequencies, was associated with a decrease in developed (systolic) tension in accordance with the negative force‐frequency relation inherent in the rat heart. When evaluated at a single diastolic tension and pacing frequency, IRANF release was positively correlated with systolic tension. ANF released under in vitro conditions was approximately 3,000 Da, in agreement with the size of the physiologically circulating form. In atria from reserpinized rats, evidence for involvement of catecholamines in chronotropicstimulated ANF release was suggested. The presence of lidocaine (5×10−4M) had no effect on rate‐induced ANF release was suggested. The presence of lidocaine (5×10−4M) had no effect on rate‐induced ANF secretion. Therefore, chronotropic stimulation releases ANF independently of changes in atrial stretch. The magnitude of this response depends on a combination of pacing frequency and diastolic tension. Catecholamine release and sodium transport through channels sensitive to a local anesthetic appear to play a minor role in rate‐dependent ANF release in vitro. (Circulation Research1989;64:799‐805)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;It has been shown previously that serotonin stimulates the production of prostacyclin by bovine aortic smooth muscle cells in culture, via 5‐HT2receptors (Coughlin SR, Moskowitz MA, Antoniades HN, Levine L.Proc Natl Acad Sci USA1981;78:7134‐7138). These cells express a synthetic phenotype, whereas the majority of the smooth muscle cells in the media from adult arteries are in a contractile state. We have now compared 5‐HT stimulated prostacyclin production in bovine aortic media explants, a preparation of contractile smooth muscle, with cultured smooth muscle cells derived from the explants. In the 1‐10 &mgr;M range, serotonin stimulates the release of prostacyclin from the explants of bovine aortic media, cultured for a short period. In the presence of cocaine (30 &mgr;M), 1 &mgr;M was sufficient to produce a maximal effect. The stimulatory action of serotonin was sustained with time and did not induce a lasting desensitization. The effect of serotonin on the explants was inhibited only partially (±30%) by ketanserin, a selective and potent 5‐HT2antagonist. It was mimicked by 5‐carboxamido‐tryptamine, a 5‐HT1agonist, but was only weakly inhibited by methiothepin, a 5‐HT1antagonist. As expected, in cultured smooth muscle cells, 5‐carboxamido‐tryptamine was only a weak agonist in stimulating prostacyclin production. In conclusion, it appears that the serotonin effect on prostacyclin production is mediated by different receptors in media explants from bovine aortic media and cultured cells obtained by outgrowth from these explants: a 5‐HT2receptor in the smooth muscle cells in culture and a receptor presenting some similarities with 5‐HT1receptors in the explants. (Circulation Research1989;64:806‐813)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;In rats injected with the toxin monocrotaline, altered synthesis and distribution of pulmonary artery elastin suggest that increased elastase activity may be important in the development of vascular changes and progressive pulmonary hypertension. To test this hypothesis, male Sprague‐Dawley rats (250‐300g) were given 40 mg/kg of the elastase inhibitor SC‐39026 in a carboxymethylcellulose vehicle or vehicle only by gavage, 12 hours before and twice daily for 8 days after a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline. Thirteen days after injection, indwelling cardiovascular catheters were inserted under pentobarbital anesthesia, and at 15 days after injection, pulmonary and systemic hemodynamic measurements were recorded with the animals awake. At post‐mortem examination, the lungs were perfused and morphometric techniques applied for light and electron microscopic evaluation. Saline‐injected rats given either SC‐39026 or vehicle were similar in all features assessed. In contrast, monocrotaline‐injected rats given SC‐39026 had significantly lower mean pulmonary artery pressure than those given vehicle (21.0±1.6 vs. 27.5±0.8 mm Hg,p<0.05), and this correlated with a significant reduction in the number of abnormally muscularized arteries at alveolar wall level (r2=0.89,p<0.001). SC‐39026 did not significantly reduce monocrotaline‐induced medial hypertrophy of muscular arteries, endothelial injury, and associated subendothelial edema; nor was there a significant increase in the proportion of the medial elastin, although a trend was apparent. Additional groups of monocrotaline injected rats were followed 3 weeks after injection, but both SC‐39026 and vehicle‐treated rats were similar at this point. Our data suggest that increased serine elastase activity associated with endothelial injury may mediate early abnormal pulmonary vascular smooth muscle differentiation resulting in muscularization of normally nonmuscular peripheral arteries and pulmonary hypertension induced in rats by injection of the toxin monocrotaline. Lack of persistence of this protective effect suggests that there may be continued elastase activity in this model. Failure to inhibit medial hypertrophy with SC‐39026 suggests that a different mechanism or a different elastase may be involved in this structural change. (Circulation Research1989;64:814‐825)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID