ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The X-linked enzyme, glucose-6-phosphate dehydrogenase (G-6-PD) was used as a cellular marker to study the clonal characteristics of human atherosclerotic lesions from females heterozygous for G-6-PD isoenzymes. Portions of uninvolved aortic wall contained both isoenzyme types (A and B), and their isoehzyme patterns were used to establish criteria for polyclonal lesions. Portions of uterine leiomyomas contained predominantly one isoenzyme type (either all A or all B) and their isoenzyme patterns were used to establish criteria for monoclonal lesions. These techniques were used to address three questions concerning atherogenesis. First, evidence for the monoclonal origin of fibrous-capped plaques was provided by the findings that small plaques had G-6-PD isoenzyme distributions similar to those of leiomyomas; that in large plaques with multiple portions assayed for G-6-PD, a large proportion (25 of 26, 96%) of plaques had monoclonal characteristics; and that multiple monoclonal portions were present in the same plaque. Second, the role of the fatty streak as a precursor of fibrous plaques was supported by the demonstration that a proportion (11 of 66, 16.7%) of fatty streaks contained isoenzyme patterns intermediate between those of polyclonal uninvolved aortic wall and monoclonal leiomyomas. Increased cellularity of fatty streaks correlated with increased deviation of isoenzyme pattern toward monoclonality. Third, the assay of portions of both small and large plaques provided no evidence for clonal selection as plaques increase in size.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Eight normal male subjects were placed on a constant 10 mEq sodium, 60 mEq potassium diet for 5 days. At 8:00 a.m. on the 5th day, the subjects were given a standard dose of 100 mEq of sodium orally or intravenously. Subjects receiving oral sodium also received 200 ml of 5% dextrose in water intravenously, and those receiving intravenous sodium also received placebo capsules orally. Water intake and posture were controlled. The subjects then returned to a free diet for 1 month and subsequently were restudied by using the opposite route of sodium administration. The subjects given the oral sodium load excreted greater quantities of sodium in their urine than those repleted intravenously. The differential natriuresis was significant as early as 2 hours after sodium loading. Plasma aldosterone concentration was similar irrespective of the route of sodium administration. Six patients with primary adrenocortical insufficiency and documented hypoaldosteronism were studied with the same protocol after 5 days of 50 mEq sodium, 60 mEq potassium intake. They also had significantly greater natriuresis after oral than intravenous sodium administration. The data suggest the presence of a splanchnic input monitor for sodium which partially regulates renal sodium excretion and is not dependent upon a turn-off mechanism for aldosterone secretion.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

We examined the effect of L-dopa, after peripheral L-amino acid decarboxylase inhibition, on sympathetic nerve activity (SNA) and blood pressure in spontaneously hypertensive rats (SHR) and in normotensive control rats. L-Dopa reduced SNA in both groups of animals. The SHRs were significantly more sensitive to the depressor effect of L-dopa than were the control animals, the threshold dose for reduction of SNA being 3 mg/kg in SHR and 15 mg/kg in control rats. Similarly, the magnitude of inhibition of SNA was substantially greater in the SHR than in normotensive rats. The reduction in SNA in the SHR was accompanied by a parallel fall in blood pressure. In contrast, blood pressure in control rats did not change significantly, even though SNA was diminished. Studies of the penetration of L-dopa into the cerebral parenchyma revealed that equivalent amounts of the amino acid entered the brains of the two groups of rats. These results suggest that the SHRs are more sensitive to the SNA-inhibiting effects of L-dopa than are normotensive rats. In addition, they confirm our previous suggestion that excessive SNA plays a causative role in the hypertension of the SHR.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

We studied the effects of acetylcholine (ACh) on small bundles of canine cardiac Purkinje fibers exposed to normal, or low-chloride (isethionate) Tyrode's solution in a rapid superfusion system. In superfusate containing 4 mM K+, the resting potential of Purkinje fibers may be either “low,” near −40 mV, or “high,” near —90 mV. ACh, at 10−6to 10−5M, increased the membrane potential from both the low and high resting levels and, in low-Cl solution, often induced a maintained shift in potential from the low to the high level. The increase in membrane potential caused by ACh was greater at the low than at the high level. ACh, at 10−6to 10−5M, reduced action potential duration in both normal and low-Cl Tyrode's solution, the effect being more marked in the latter. These effects of ACh were reversibly abolished by atropine (5 × 10−5M), indicating that they were mediated via muscarinic ACh receptors, and they probably result from an increase in membrane K+ conductance since 10″5 M ACh reversibly reduced, by 13% on the average, the amplitudes of the steady changes in membrane potential evoked by applying small current pulses (-5 to — 25 nA, 200 msec). ACh (10−5M) also diminished the rate of, or stopped, spontaneous activity arising from either level of membrane potential. The cessation of spontaneous slow response activity, arising from the low level, sometimes was accompanied by a maintained shift of the membrane potential to the high resting level. It is concluded that the action of ACh on Purkinje fibers is qualitatively similar to its action on sinoatrial nodal and atrial cells.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The effects of ouabain or ouabain and furosemide on renal function and renin secretion were studied in conscious isovolemic sheep. The sheep received a continuous renal arterial infusion of papaverine, 7 mg/min, throughout the experiment. Ouabain alone (7 × 10−7M in the renal plasma) produced significant decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) but not in renal perfusion pressure. Plasma [K+] rose after ouabain administration. Fractional (FENa) and absolute (UN.V) Na+excretion were 2.9 ± 1.0% (mean ± SE) and 78 ± 54 μEq/min, respectively, during the papaverine infusion and rose to 19 ± 5.1% (P< 0.05) and 528 ± 116 μEq/min (P< 0.01) after ouabain administration. Despite the large changes in Na+ reabsorption, renin secretion was not stimulated. During the control period, renin secretion was 281 ± 131 ng/min and the average renin secretion after ouabain administration was 310 ± 78 ng/min (not significant). A smaller dose of ouabain (2 × 10−7M) infused into the renal artery with 40 mg of furosemide, iv, did not decrease GFR but RPF was suppressed. FENa and UNBV averaged 4.4 ± 1.6% and 121 ± 44 μEq/min, respectively, while papaverine was infused into the renal artery and increased to 18 ± 4.8% (P< 0.05) and 636 ± 209 μEq/min (P< 0.05) after ouabain and furosemide were infused. Renin secretion was 118 ± 62 ng/min during the control period and averaged 240 ± 67 ng/min after ouabain plus furosemide. The difference was not statistically significant. Thus ouabain alone does not stimulate renin secretion in the conscious, isovolemic sheep despite a presumed increase in [NaCl] at the macula densa and inhibition of NaCl transport by the loop of Henle. Ouabain also blocks the normal stimulatory effects of furosemide on renin secretion.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

To determine whether left ventricular hypertrophy (LVH) altered total and regional coronary blood flow, we inflated a balloon around the ascending aorta of nine dogs; six acute and six sham-operated dogs were controls. After 6 weeks, all dogs were studied with an open chest under anesthesia; the balloons were deflated. There was moderate LVH as shown by increased left ventricular weight and fiber diameter. At rest there were no major differences of coronary flow or resistance per gram of muscle. With maximal coronary vasodilation due to adenosine or carbochrome, mean coronary vascular resistance was 84% higher in LVH than in normal hearts; with isoproterenol, resistance was 54% higher in LVH. These changes were similar in right and left ventricles. Minimal coronary resistance at end diastole also was higher in LVH—64% and 94% for the two sets of vasodilators, respectively. There were no significant differences in capillary or large vessel proportional volumes in LVH and control dogs, but arterial capacity could not be estimated. The raised minimal coronary resistance suggests the possibility that, with stress, coronary flow, especially to subendocardial muscle, might be inappropriate and perhaps cause ischemic damage. However, the changes noted might have been due to coronary arterial responses to raised coronary pressures rather than to hypertrophy itself.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Aortic pulse wave velocity was determined in Macaca fascicularis monkeys fed either atherogenic or control diets for 36 months. The foot-to-foot velocity and apparent phase velocities of the second through seventh Fourier harmonics at a given diastolic pressure in the atherosclerotic monkeys were 1.5 to 2.0 times the values for the control animals. More than 80% of the aortic intimal surface of the atherosclerotic monkeys was covered with fibrous or fatty plaque, which approximately doubled wall thickness and wall thickness to radius ratio. Angiochemical evaluations showed no difference in collagen or elastin concentration (as a fraction of lipid and mineral-free dried aorta), but the atherosclerotic aortas were 1.5 to 2.0 times that of control in collagen and elastin content (defined as the absolute quantity beneath a square centimeter of intimal surface). Total cholesterol and calcium concentrations in the atherosclerotic aortas were more than 10 times the values for the control aortas. The static circumferential distensibility of the excised atherosclerotic aortas was significantly less than control, but there was no difference in incremental (Young's) modulus of elasticity. The in vitro pressure-strain elastic modulus of the atherosclerotic aortas was more than twice that of control, which was predicted from the enhanced wave velocity. The significantly increased stiffness of the atherosclerotic arteries appeared to be due mainly to the increased wall thickness caused by the atherosclerotic plaques rather than to material changes described by Young's modulus. Extensive medial damage, however, also was present and could have had a major influence on stiffness. Atherosclerosis therefore can result in increased aortic stiffening, detectable by pulse wave velocity, even if there is no change in the overall Young's modulus of elasticity.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Computerized techniques were employed to generate alternating anodal and cathodal or sequential anodal strength-interval curves during and following 15-minute coronary artery ligations in 14 anesthetized dogs. The right atrium was paced at 2.5 Hz, and unipolar ventricular strengthinterval curves with simultaneous conduction times were recorded every 45-120 seconds during ischemia and reperfusion. Within 1-2 minutes of ligation, anodal midcurve and late diastolic thresholds fell sharply, and cathodal thresholds fell slightly or changed little. After 5 minutes of ischemia, anodal thresholds remained low, cathodal thresholds rose, and conduction times increased. At 10–15 minutes of ligation, if the ischemic zone was small, anodal thresholds were low, often approaching cathodal values, and conduction returned toward control values. When the ischemic zone was large, unipolar thresholds and conduction times increased late during the ligation period. Throughout the course of ischemia, the falling limb of the strength-interval curve shifted progressively to the left indicating shorter refractory periods. Following abrupt reperfusion, anodal phase 3 dips promptly reappeared; refractory periods returned toward control, and supernormal conduction was noted. By 3-5 minutes of reperfusion, the falling limb of the strength-interval curve had shifted to the right of control and conduction times increased. Thus, vulnerability to arrhythmias during early ischemia (i.e., 5 minutes) is characterized by low anodal midcurves and late diastolic thresholds, short refractory periods, and slow conduction. During the first minute of reperfusion, anodal excitability is increased during the early dip and conduction times are supernormal. Increases in anodal excitability correlate better with the peak incidence of early ligation and reperfusion arrhythmias than do changes in cathodal excitability.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Morphometric data from stable (nonedematous) isolated dog lungs, perfused with nearly cell-free perfusates, were compared to similar stereological evaluations of isolated dog lungs after induction of severe acute hydrostatic edema. In the edematous lungs, capillary surface and volume densities were substantially increased. Alveolar surface density was also increased. Thicknesses of the endothelial and type I epithelial cellular compartments of the air-blood barrier were unchanged. Thickness of the interstitial compartment of the air-blood barrier was substantially increased and this, in turn, caused an overall increase in mean thickness of the barrier. Volume densities of the nonparenchymal connective tissue spaces surrounding the extra-alveolar vessels and airways were also increased. In both the endothelial and type I epithelial cells, cytoplasmic volume densities of pinocytotic vesicles were increased. In addition, the number of vesicles opening onto the luminal and albuminal cellular surfaces increased significantly. Transendothelial vesicular passage may contribute to interstitial edema formation, and transepithelial vesicular transport may contribute to alveolar flooding in isolated perfused dog lungs.

ISSN:0009-7330    

出版商:OVID    

年代:1978

数据来源: OVID