ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of cholesterol-feeding in the presence of dipyridamole (0.60 g daily) on contractile responses and on endothelium-dependent and endothelium-independent relaxations in isolated rabbit aortas are described. The investigations were performed simultaneously with those described in Part ICire Res1986;58:552–564), where the effects of cholesterol feeding on vascular reactivity in rabbit arteries (n= 8 in each group) selected at random from the same group of animals was studied. In the hypercholesterolemic rabbits treated with dipyridamole for 8 or 16 weeks, both the increases in plasma cholesterol and the formation of fatty streaks were significantly less pronounced than in the hypercholesterolemic rabbits not receiving the drug. Segments of the isolated arteries were mounted in organ chambers for isometric tension recording. The contractions caused by acetylcholine, prosta-glandin F^, norepinephrine, clonidine, and serotonin and the endothelium-independent relaxations to nitroglycerin were not significantly altered by the hypercholesterolemia in rabbits treated with dipyridamole, even after 16 weeks of treatment. Thus, the decreased responses to norepinephrine, clonidine, and nitroglycerin and the augmented responses to serotonin noted in aortas of hypercholesterolemic rabbits in Part I were absent in the dipyridamole-treated hypercholesterolemic animals. The endothelium-dependent relaxations to ATP and acetylcholine were not affected after 8 weeks of hypercholesterolemia in presence of dipyridamole, while after 16 weeks the relaxations to ATP and acetylcholine were attenuated only in the more severely affected arteries. The effects of hypercholesterolemia + dipyridamole on endothelium-dependent relaxations were significantly less pronounced than those induced by hypercholesterolemia alone. We thus conclude from our studies that in the rabbit 1) dipyridamole can partially inhibit the augmentation in plasma cholesterol levels caused by a cholesterol-rich diet; 2) dipyridamole can slow down the process of formation of intimal aortic lesions caused by the cholesterol feeding; 3) dipyridamole inhibits the cholesterol-induced changes in vascular reactivity, and 4) the degree of formation of intimal aortic lesions determines the degree to which the vascular responses, especially the endothelium-dependent relaxations, are affected by the cholesterol-rich diet.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Velocity profiles were determined in rabbit mesenteric arterioles (diameter 17–32 &mgr;m). A good spatial resolution was obtained by using the blood platelets as small and natural markers of flow, providing for the first time in vivo detailed, quantitative information about the shape of the velocity profiles in microvessels. In some experiments red blood cell velocity profiles were recorded as well. Easy detection of the cells of interest could be achieved by labelling them selectively with a fluorescent dye and visualizing them by intravital fluorescence video microscopy, using flashed illumination. Pairs of flashes were given with a short, preset time interval between both flashes, yielding in one TV picture two images of the same cell displaced over a certain distance for the given time interval. Velocity and mean radial position of cells, flowing within an optical section around the median plane of the vessel, were determined. The shape of the velocity profiles of platelets and red blood cells was similar. The profiles were flattened as compared to a parabola, both in systole and diastole. Vessel diameter did not change measurably during the cardiac cycle. As an index of the degree of blunting of the profiles, the ratio of the maximal and mean velocity of the profile was used, which is 2 for a parabola and 1 for complete plug flow. The index ranged from 1.39 to 1.54 (median 1.50), and increased with vessel diameter. Calculations showed that the blunting of the profiles cannot be explained by an influence of the finite depth of the optical section.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Changes in diastolic chamber distensibility (DCD) during hypoxemia and ischemia were studied in isolated-buffer-perfused rabbit hearts. Two minutes of hypoxemia (low Po2coronary flow) resulted in a shift of the diastolic pressure-volume curve to the left, i.e., distensibility was decreased (hypoxemic contracture). In contrast, 2 minutes of ischemia (zero coronary flow) resulted in an initial shift of the diastolic pressure-volume curve to the right indicating increased distensibility, which was followed by a later (30 minutes) shift to the left (ischemic contracture). Two minutes of ischemia superimposed on hypoxemia caused complete reversal of contracture. A quick stretch and release applied to the myocardium reversed late ischemic contracture but did not effect early hypoxemic contracture. The role of intracellular pH in modulating changes in DCD during hypoxia and ischemia was studied using phosphorus-31 nuclear magnetic resonance spectroscopy of isolated-buffer-perfused rat hearts that demonstrated changes in DCD similar to rabbit hearts during hypoxemia and ischemia. Intracellular pH decreased from 7.03 ± 0.02 to 6.87 ± 0.03 (p < .01) during 2 minutes of ischemia but did not change significantly during 4 minutes of hypoxemia. When 2 minutes of ischemia were superimposed on hypoxemia, pH decreased from 6.99 ± 0.01 during hypoxemia to 6.88 ± 0.02 after 2 minutes of ischemia (p < .01), concomitant with the complete reversal of hypoxemic contracture. These results suggest different mechanisms for late ischemic and early hypoxemic contracture and also suggest an explanation for the opposite initial changes in DCD seen after brief periods of ischemia and hypoxemia. The early development of contracture during hypoxemia and rapid redevelopment of diastolic tension after quick stretching are consistent with the hypothesis that hypoxemic contracture results from persistent Ca-activated diastolic tension secondary to impaired calcium resequestration by the sarcoplasmic reticulum. In contrast, the late development of contracture during global ischemia and reversal by quick stretching is compatible with rigor bond formation. The initial increase in distensibility during early ischemia and the reversal of hypoxemic contracture by a brief period of superimposed ischemia probably is the result of two factors present during ischemia but not during hypoxemia: 1) the collapse of the coronary vasculature and loss of the "erectile" effect and, 2) the rapid development of intracellular acidosis, which has been shown to affect myofibrillar calcium sensitivity, and this may lead to a decrease in Ca++activated diastolic tension.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Recent evidence suggests that dopamine may alter kidney function by actions not only in the renal vasculature but also at the glomerular-mesangial level. We studied this phenomenon by examining the ability of dopamine to antagonize the contractile properties of angiotensin II hi isolated rat glomeruli and cultured mesangial cells. In isolated rat glomeruli angiotensin II caused a decrease in the planar surface area, indicating glomerular contraction, an effect that was abolished by coincubation with dopamine. Angiotensin II also mediated shape changes in cultured mesangial cells, which resulted in a decline in their planar areas. Simultaneous addition of dopamine prevented these decreases in cell size. In mesangial cells grown on a flexible silicone rubber support, angiotensin II addition enhanced wrinkling of the mobile surface. This indicated that the angiotensin-II-induced decrease in cell size observed in cells grown on conventional substrata represented contraction. Conversely, dopamine caused a rapid reduction in wrinkling of the surfaces from control cells as well as those previously treated with angiotensin II, actions consistent with cell relaxation. The prostaglandin inhibitor indomethacin did not alter the ability of dopamine to attenuate angiotensin-II-associated reductions in mesangial cell surface area. Direct determination of mesangial cell prostaglandin-E2production showed that dopamine did not change either basal synthesis or angiotensin-II-stimulated synthesis of prostaglandin. The results demonstrate that dopamine antagonizes the constrictor effect of angiotensin II at the glomerular-mesangial level. This action of dopamine is prostaglandin independent. These findings support a role for dopamine in the regulation of glomerular filtration and may provide a rationale for its use during states of renal, vasoconstriction.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The influence of sympathetic innervation on the growth and intrinsic rate of beating established by fetal rat heart was studied by culturing fetal atrial tissue in sympathetically innervated and denervated anterior eye chambers of adult Sprague-Dawley rats. One anterior eye chamber in each host rat was sympathetically denervated by removing the ipsilateral superior cervical ganglion.In oculo, atrial grafts were vascularized by blood vessels sprouting from the his and innervated by sympathetic and parasy mpathetic fibers from the ground plexus of the iris. Innervation was assessed by light-activated efferent nerve stimulation to the grafts that changed their rates of beating. The norepinephrine contents of 16 atria cultured for 2.5 months in sympathetically innervated and denervated eye chambers were 5.7 ± 1.1 ng/implantvs. 0.2 ± 0.07 ng/implant (mean ± SEM), indicating permanent sympathetic denervation of the anterior eye chamber and the implanted atria. By 8 weeksin oculo, atria maturing in sympathetically innervated anterior eye chambers were 86% larger than those hi denervated eye chambers (2.22 ± 0.29 vs. 1.19 ± 0.13 mm2); the weight of innervated transplants was over 3 tunes that of noninnervated grafts (2.35 ± 0.75 vs. 0.76 ± 0.21 mg). After implanted atria had ceased growing rapidly (2.5 monthsin oculo), bipolar electrodes were implanted adjacent to the cornea to record impulses from atrial grafts while host rats were unanesthetized. The dark-adapted baseline heart rates of sympathetically innervated and noninnervated atria were virtually identical (289 vs. 290 bpm). Graft intrinsic heart rate was estimated by combined β-adrenergic and muscarinic receptor blockade with atenolol (1.0 mg/kg) and methylatropine (10 &mgr;g/kg). Sympathetically innervated transplants hadlowerintrinsic heart rates than noninnervated atria (134 ± 25 vs. 213 ± 12 bpm). These data suggest that sympathetic innervation of the developing heart influences both growth and intrinsic rate of beating.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Neural crest cells are known to contribute to the normal architecture of the heart and aortic arch arteries. Ablation of neural crest cells over somites 1 to 3 in the chick embryo prevents conotruncal septation and results in persistent truncus arteriosus. To determine whether a deficiency of cardiac neural crest cells produces hemodynamic changes prior to the development of identifiable structural defects in the heart, we measured dorsal aortic blood velocity and vitelline artery blood pressure in lesioned and control embryos at a period of cardiac morphogenesis prior to septa! formation. The internal diameter of the dorsal aorta at the level of the sinus venosus and the internal diameter of the aortic arch arteries at their midpoints were measured in embryos at Stage 18 of development using a filar micrometer eyepiece and a dissecting microscope. Embryos with neural crest lesions had significantly greater dorsal aortic blood flow velocity than control embryos. In addition, embryos lacking cardiac neural crest had significantly lower systolic and diastolic blood pressures than control embryos. There was no difference in heart rate, dorsal aortic diameter or internal diameter of the aortic arch arteries between lesioned and control embryos. Scanning electron micrographs revealed no gross morphological differences in cardiac looping or conotruncal wall development between lesioned and control embryos; however, embryos with cardiac neural crest ablations developed markedly hypoplastic 4th pharyngeal arches. This data suggests that hemodynamic changes precede the onset of structural heart defects in embryos with cardiac neural crest ablations.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Cardiac hypertrophy due to a chronic hemodynamic overload is accompanied by isoformic changes of two proteins of the thick filament of the sarcomere, myosin, and creatine phosphoklnase. We have looked for isoactin changes, using deoxyribonucleic acid probes complementary to α-skeletal and α-cardiac actin messenger ribonucleic acids. Three groups of rats were studied at various days after application of a pressure overload (2–4 days,n= 13, 8–15 days,n= 5, and 30–40 days,n= 7) and were compared to control animals(n= 11). Whereas α-skeletal actin messenger ribonucleic acids were hardly detectable in the normal hearts (0.6 ± 0.16%), they accumulated significantly in the first 4 days after the aortic stenosis (4.6 ± 3.1%,p< 0.001 vs. controls) and then slowly declined (8–15 days, 3.2 ± 1.7% and 30–40 days, 1.6 ± 0.6%, p < 0.05 and NS vs. controls). This figure is similar to that observed in 8-day-old rats (2.27 ± 0.3%,p< 0.01 vs. controls). We conclude that, in rat myocardium, the expression of messenger ribonucleic acids encoding the sarcomeric actins is altered at the onset of a pressure overload hypertrophy. Although the physiological significance of isoactin changes is unknown, our results show that the thin filament participates as well as the thick filament in the response of cardiac muscle to new functional requirements.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Some of the mechanical characteristics of papillary muscles and trabeculae (n= 14) isolated from the free wall of the right ventricle of dogs were compared to those obtained from the free wall of the left ventricle (n= 14). Peak total tension (7.2 ± 1.6 versus 7.9 ± 1.7 g/mm2,p= NS) and peak velocity of tension development (31 ± 8 vs. 28 ± 4 g/mm2/sec, p = NS) were similar in both groups of muscles. However, right ventricular muscles shortened faster over nearly all loading conditions, and during isometric contraction, their time to attain peak total tension was shorter (336 ± 26 vs. 401 ± 42 msec,p< 0.005) than that of left ventricular muscles. Varying stimulation rates (6, 12, 24, and 36 stimuli/min), increasing calcium concentration from 2.54 to 6.35 mM or adding norepinephrine 50 &mgr;M, did not significantly alter these differences. There were no differences in myosin isozymes (V1, V2, or V3) between ventricles to explain these differences. These results indicate that important mechanical differences exist between right and left ventricular myocardium and that these differences should be considered when extrapolations are made from myocardium of one area of the heart to another.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The possibility that the prostanoid system contributes to the capability of the newborn piglet to maintain cerebral blood flow and cerebral metabolic rate during hypotension was investigated. The effect of hemorrhage on net (arterial-to-venous) cerebral prostacyclin production and the effects of indomethacin on cerebral hemodynamic response to hemorrhage and on the cerebral oxygen utilization following hemorrhage were determined in chronically Instrumented, unanesthetized newborn pigs. Hemorrhage decreased arterial pressure about 35% but did not affect cerebral blood flow or cerebral O2 consumption. Hemorrhage was accompanied by an increase in net cerebral 6-ket0-PGFlα production from 4.0 ±1.1 to 15.3 ± 4.9 ng/100gmin (mean ± SEM). Indomethacin treatment of piglets following hemorrhage inhibited the net cerebral production of 6-keto-PGFla and caused a decrease in blood flow (= 40%) to all brain regions within 20 minutes. The decrease in cerebral blood flow was the result of an increase in cerebral vascular resistance of 57 and 180%, 20 and 40 minutes post treatment, respectively. Cerebral O2 consumption was reduced from 2.5 ± 0.3 ml/100 g. min to 1.5 ± 0.3 ml/100 gmin 20 minutes following treatment of hemorrhaged piglets with indomethacin and to 1.1 ± 0.3 ml/100 g. min 40 minutes after treatment. Six of 8 piglets for whom the data were recorded that were administered indomethacin following hemorrhage became comatose with cerebral O2 consumption of 0.4 ± 0.1 ml O2/100 g-min by 40 minutes after treatment. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID