ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

This study demonstrates endothelium-dependent relaxation in the surface arterioles of the brain. A helium-neon laser was used to injure endothelium in situ following i.v. injection of Evans blue dye, which sensitizes the bed to the laser. Areas 18 or 36 μm in diameter were injured and no longer relaxed to either 1 ml of acetylcholine chloride or bradykinin triacetate, 80 μg/ml delivered for 60 seconds. Dilations to sodium nitroprusside (30 μ.g/ml) were unaffected. Normal responses to nitroprusside, plus electron microscopy, established that vascular smooth muscle was uninjured. Endothelium-dependent relaxation was impaired when only minor ultrastructural damage was present. Dilation was inhibited downstream and upstream as far as 80 μm from the center of the laser beam. This suggests a spread of endothelium injury around the site of laser impact. However, inhibition was somewhat more marked downstream than upstream, implying that a portion of the downstream response was dependent on a substance released from an upstream site. To date, very few studies have reported endothelium-dependent relaxation in vivo, especially in the microcirculation. The present study accomplishes this. Moreover, in contrast to in vitro observations of endothelium-dependent relaxation in large vessels, the in vivo elimination of endothelium-dependent relaxation in the microcirculation required neither removal of endothelium nor injury to large numbers of endothelium cells. Since endothelium-dependent relaxation in the microcirculation has now been demonstrated using three different techniques to injure endothelium, it is reasonable to conclude that the phenomenon is real.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

An improved assay was used to investigate the effects of hypoxia or ischemia on interstitial fluid and coronary venous effluent levels of adenosine in isolated perfused nonworking rat hearts. The adenosine in 5- to 10-μl samples of left ventricular epicardial surface transudates and coronary effluents was reacted with chloroacetaldehyde, and the fluorescent derivative (l, A6-ethenoadenosine) was quantitated using high pressure liquid chromatography and fluorescence detection. Hearts responding to hypoxia could be separated into two groups. In one group of hearts, the control (normoxic) transudate and effluent adenosine concentrations were 94 ± 24 and 41 ± 6 pmol/ml, respectively. These values increased by 118 and 96%, respectively, with 5 minutes of hypoxia (30% O2, and returned to control levels 5 minutes after resumption of normoxia. In a second group of hearts, the normoxic control levels of adenosine in the transudates (42 ± 7 pmol/ml) and coronary effluents (62 ± 17 pmol/ml) were increased with hypoxia by 174 and 1,178%, respectively. However, the transudate levels continued to rise for 5 minutes after resumption of normoxic perfusion while effluent levels fell. In another series of hearts, global ischemia for 30 seconds elicited an elevation of transudate adenosine levels by 362 to 641 % above control (58 ± 15 pmol/ml) as determined 30 seconds after resumption of perfusion flow. These data suggest that 1) the adenosine concentration in the interstitium of the oxygenated nonworking rat heart is 4 × 10−8to 1 × 10−7M, and 2) coronary effluent levels of adenosine neither accurately reflect the absolute magnitudes of interstitial adenosine to which myocardial cells are exposed nor consistently parallel changes in interstitial adenosine levels that may occur with alterations in oxygen delivery.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Sodium pump Inhibition in cardiac muscle cells is associated with changes in intracellular sodium, calcium, and hydrogen concentrations as well as in membrane ion transport activity. We examined further the functional relations among these entities using cultured chick ventricular cells. [Ca]1 and pH, were determined from fluorescence signals obtained from cells loaded with fura-2 or BCECF, respectively. Ouabain (100 μM) elevated [Ca]1 eightfold and decreased pH, by 0.11 unit (a 30% increase in [H+]). In the presence of 10 μM ethylisopropylamiloride, a potent inhibitor of Na-H exchange, ouabain elevated [Ca]1 3.5-fold and reduced pH, by 0.16 unit (a 48% increase in [H +]). Exposure to sodium-free (sodium replaced with potassium) medium produced a twelvefold increase in [Ca], and a 0.12 pH unit decrease in pH1. In cells treated with 100 μM ouabain, exposure to sodium-free (lithium) medium resulted in a 22-fold sustained increase in [Ca], and a rapid intracellular acidification (pH 7.15 to 6.60). The effect of ouabain or sodium-free medium on pH1 was abolished in calcium-free medium; addition of 1 mM Ca rapidly increased [Ca]1 and decreased pH1. In cells treated with subtoxic (3 μM) or toxic (100 μM) concentrations of ouabain, initial 24Na uptake rates were significantly greater than in control cells and were significantly reduced in the presence of 10 μM ethylisopropylamiloride. We conclude that ouabain (100 μM) produces 1) intracellular acidification as a result of sodium pump inhibition; 2) calcium accumulation via Na-Ca exchange, and 3) subsequent Ca-H interaction within the cell. The decrease in pH, stimulates H+ efflux and Na+ influx via Na-H exchange to limit further decline in pH1 and to further augment [Na]1, which tends to elevate [Ca]1 as a result of increased calcium accumulation via Na-Ca exchange. Thus, Na-H exchange may play an important role in the positive inotropic and also the toxic effects of cardiac glycosides.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The release of endogenous noradrenaline and its deaminated metabolite dihydroxyphenylglycol in the myocardium have been studied in the isolated perfused heart of the rat subjected to three models of energy depletion: ischemia, anoxia, and cyanide intoxication. Anoxia and cyanide intoxication were combined with substrate deficiency at constant perfusion flow. All three energy-depleting procedures caused a similar overflow of noradrenaline which, following a constant delay of 10 minutes without increased release, amounted to more than 25% of total heart content within 40 minutes. This noradrenaline overflow was not diminished in the absence of extracellular calcium and was inhibited by the uptake1blocker deslpramine in all three experimental models, indicating a common and nonexocytotic release mechanism. In the presence of glucose, neither anoxia nor cyanide intoxication resulted in a measurable noradrenaline overflow. Conversely, blockade of glycolysis or glucose depletion prior to ischemia or cyanide poisoning accelerated the noradrenaline overflow, demonstrating a key role of the sympathetic nerve cells' energy status in causing nonexocytotic catecholamine release. Blockade of energy metabolism in the presence of oxygen (cyanide model) resulted in the overflow of high amounts of dihydroxyphenylglycol that was not inhibited by uptake, blockade. The release of the lipophilic dihydroxyphenylglycol by diffusion reflects deamination of axoplasmic noradrenaline by monoamine oxidase. Since saturation of the enzyme could be excluded in this model dihydroxyphenylglycol release can be taken as a mirror of cytoplasmic noradrenaline concentration. The results obtained by these studies indicate that nonexocytotic catecholamine release is a two-step process induced by energy deficiency in the sympathetic varicosity. In a first step, noradrenaline is lost from storage vesicles, resulting in increasing axoplasmic concentrations. The second step is the rate-limiting transport of intracellular noradrenaline across the cell membrane by the uptakeicarrier that has reversed its normal net transport direction.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

As yet there is no model or simulation that accounts for the anisotropic difference in the shape of the upstroke and safety factor of propagating cardiac action potentials: fast upstrokes occur with slow transverse propagation and slow upstrokes occur with fast longitudinal propagation. The purpose of this paper is to demonstrate, however, that a simplified cable model based on directional differences in the effective membrane capacitance predicts in detail the experimentally measured directionally dependent behavior of the upstroke in response to modification of the sodium conductance. Quinidine and lidocaine produced greater relative decreases in Vra, and conduction velocity with longitudinal propagation than with transverse propagation, as predicted on the basis that the shape differences should produce an anisotropic distribution in the membrane uptake of sodium channel binding drugs. The simulation predictions of the effects of positive shifts of the take-off potential due to premature action potentials were also confirmed experimentally: there was a greater relative decrease in conduction velocity, Vvmx, and Vvmx,,(tm) with a greater increase in xfootduring longitudinal propagation than with transverse propagation. The major anisotropic differences in shape occurred when the take-off potential approached the least negative value that produced a propagated response. The extensive experimental verification of the results of a simplified model based on directional differences of effective membrane capacitance, combined with directional differences in effective axial resistivity, provides an initial quantitative basis for the anisotropic behavior of propagating depolarization in response to modification of the sodium conductance in cardiac muscle.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The distribution of serotonin (5-HT)-like immunoreactive (5-HT-LI) nerves and the potential role of 5-HT as a vasoconstrictor transmitter in large cerebral arteries of the rabbit were examined. 5-HT-LI fibers with weak immunofluorescence were observed in the anterior cerebral, middle cerebral, and basilar arteries when fixed by immersion after dissection from exsanguinated animals. The 5-HT-LI fibers, however, were not detected in these arteries when fixed either in vitro or in situ after first being perfused with Krebs solution in situ to flush the blood component from the lumen prior to dissection. In these arteries, 5-HT-LI nerve fibers with intense immunofluorescence, however, reappeared following incubation with 5-HT in vitro. The intensity of the 5-HT-LI fibers seemed to be proportional to the duration and 5-HT concentration during incubation. Following chronic surgical sympathectomy, 5-HT-LI fibers were not detected in arteries before or after incubation with 5-HT. Transmural nerve stimulation elicited constriction in 50% of the control arterial segments examined. The constriction was not affected by ketanserin but was prevented by guanethidine and chronic surgical sympathectomy. The remaining arterial segments that did not respond on transmural nerve stimulation, however, became constrictive on transmural nerve stimulation following incubation with 5-HT in vitro. The constriction was blocked by ketanserin and clonidine. These results demonstrate that the large cerebral artery of the rabbit brain has extremely sparse or no authentic 5-HT-LI nerves. The intense 5-HT-LI nerves observed following incubation with 5-HT are primarily due to uptake of 5-HT into sympathetic nerves, and on transmural nerve stimulation 5-HT can be released to induce vasocon-striction. It is suggested that 5-HT can act as an alternative sympathetic vasoconstrictor transmitter in cerebral arteries.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Studies were performed on anesthetized 16–18 week old normotensive Wistar-Kyoto rats, spontaneously hypertensive rats, and Goldblatt two-kidney one clip renal hypertensive rats, treated from age 4–5 weeks with an oral antihypertensive regimen consisting of hydririazine, reserpine, and chlorothia-zide. Measurements of flow and intravascular pressure in the cerebral microvasculature were made via a constantly suffused open cranial window using video microscopy. A significant upward shift was seen in the pressure range for cerebral blood flow autoregulation in both groups of untreated hypertensive animals. Following treatment, the autoregulatory range in both hypertensive models was restored to a level nearly identical to control. The prevention of this shift in treated animals was due primarily to the prevention of structural microvascular adaptations that occur in untreated hypertensive animals. By preventing elevations in microvascular pressure, treatment may have eliminated the major stimulus for development of hypertrophy in resistance vessels. However, a persistent increment of arteriolar wall mass in treated spontaneously hypertensive rats may represent a hyperplastic response not influenced by treatment. Likewise, a persistent constriction of the smallest arterioles in treated renal hypertensive rats may represent a differential sensitivity of microvessels to circulating vasoactive agents. It appears that treatment initiated in the prehypertensive state, or before significant sustained hypertension has occurred, can markedly reduce the cerebrovascular morbidity associated with two different forms of hypertension.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

To determine whether the relative decline in cardiac myosin isoenzyme V, with maturation continues progressively into senescence and whether thyroxine could reverse age-associated changes in the myosin isoenzyme profile and contraction, rats 2, 8, and 24 months old were treated with thyroxine, 6.4 mg/kg, for 7 days. Myosin isoenzymes, Ca2+-myosin ATPase activities, and isometric contractile function were measured in cardiac preparations from thyroxine-treated animals and age-matched controls. Right ventricular hypertrophy did not occur with aging in controls. Thyroxine increased right ventricular weight in each age group compared to the control group. Body weight decreased by 10% in all thyroxine-treated rats. The relative right ventricular V, isoenzyme content progressively decreased from 75 ± 1% to 54 ± 1% and 14 ± 1% in controls at 2,8, and 24 months, respectively, and was associated with a reciprocal increase in V3myosin isoenzyme. Ca2+-myosin ATPase activity also progressively declined monotonically with age in the control rats from 854 ± 28 nmol Pi/mg prot/min at 2 months to 529 ± 28 nmol Pi/mg prot/min at 24 months. Thyroxine administration increased right ventricular V, at each age to 97 ±2%, 73 ± 2%, and 59 ± 2% at 2, 8, and 24 months, respectively. A thyroxine induced increase in the Ca1+-myosin ATPase activity could be detected only in the 24-month-old animals. Isometric contraction duration in thin right ventricular papillary muscles increased with age from 172 ± 4 to 180 ± 5 to 225 ± 8 ms at 2, 8, and 24 months, respectively, and was markedly shortened (p<0.001) by thyroxine at each age so that the 24-month thyroxine value was less than the 2-month control. The maximum rate of force production did not change with age in controls and was increased by thyroxine at all ages. Thus, with aging from maturation to senescence, even in the absence of right ventricular hypertrophy, there is a profound monotonic decrease in percent right ventricular V, that is paralleled by a decline in Ca2+-myosin ATPase activity. Also, neither the change in genetic expression of myosin protein synthesis nor prolonged contraction duration that occurs with aging is irreversible. Both can be modulated by thyroxine.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

This project was undertaken to determine whether electron probe x-ray microanalysis (microprobe analysis) could be utilized to determine the subcellular sites responsible for low sodium-induced calcium accumulation in myocardium. Ultrathin cryosections of rabbit papillary muscles were analyzed using microprobe analysis, and the concentrations (mmol/kg dry wt) of Na, Mg, P, S, Cl, K, and Ca were compared against low sodium (36 mM) and control (139 mM NaCl) muscle groups. Visual resolution of junctional sarcoplasmic reticulum in freeze-dried myocardial sections was achieved, and systematic analysis of junctional sarcoplasmic reticulum and sarcolemma was performed. Myofibrils and mitochondria were also analyzed. Reductions in Na and Cl concentration were measured in virtually all compartments of muscles bathed in low sodium. In addition, low sodium produced a doubling of junctional sarcoplasmic reticulum and sarcolemmal calcium concentrations (p<0.01). No significant changes in calcium were observed at other analyzed sites. The increased calcium at the junctional sarcoplasmic reticulum and sarcolemma correlates with (but may not completely account for) the threefold Increase in contractility measured after 40 minutes in low sodium concentrations. This work demonstrates that elemental changes associated with the myocardial junctional sarcoplasmic reticulum and sarcolemma are amenable to direct, in situ microprobe analysis and further defines these structures as primary sites of calcium accumulation in low sodium concentrations.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID