摘要:

Recent advances in nutritional and biochemical research have substantiated the importance ofmyo-inositol both as a dietary component and a constituent of cellular phosphatidylinositol. This work has indicated the importance of acyltransferase reactions for the enrichment of membrane phosphatidylinositol in arachidonic acid and the formation of the 1-stearoyl 2-arachidonoyl molecular species which commonly predominate in mammalian tissues. Inositol deficiency in animals has been shown to produce an accumulation of triglyceride in liver, intestinal lipodystrophy, and other abnormalities. Cellular functions elucidated for phosphatidylinositol in biological membranes include mediating cellular responses to external stimuli and serving as a source of arachidonic acid for the biosynthesis of prostaglandins including thromboxane. An alteration in inositol metabolism has been documented in patients with diabetes mellitus and chronic renal failure which has led to clinical interest in modulating dietary inositol levels in the prevention and treatment of human disease.

ISSN:0008-4212    

DOI:10.1139/y84-001

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

Calcium transporting systems and the regulatory events accompanying them are pivotal in the function of the cardiac cell. The concerted involvement of the various membranes achieve cellular calcium homeostasis that can also respond to the physiological exigencies of the cell. Three membrane systems are primarily involved; the sarcolemma, sarcoplasmic reticulum, and the mitochondria. The various Ca2+transport systems that have been described in these membranes are as follows: the calcium channel, Ca2+-ATPase, Ca2+–Mg2+ATPase, and sodium–calcium exchanger in the sarcolemma; the Ca2+–Mg2+ATPase and a possible calcium channel in the sarcoplasmic reticulum; and the sodium–calcium exchanger and electrophoretic calcium uniporter in the mitochondrial inner membrane. These systems mediate calcium fluxes to maintain physiological cytosolic calcium concentrations. β-Adrenergic hormones regulate calcium transport systems in sarcolemma and sarcoplasmic reticulum, while α-adrenergic hormones modulate those in the mitochondria and probably in the sarcolemma. The response to these hormones is initiated at the sarcolemma, which contains the specific receptors. Intracellularly the effects are propagated by secondary messengers, e.g., cAMP, calcium, and lipid changes. Specific proteins are also involved in these events. Phospholamban, a 22 000 dalton protein, is involved in mediating the cAMP-dependent inotropic effects, by activating the Ca2+–Mg2+ATPase of the sarcoplasmic reticulum. Alterations in any one of the systems involved in the regulation of calcium transport or in the calcium transport systems per se, would then result in drastic alterations in the cellular calcium homeostasis. Such effects could be of significance in cellular dysfunction during cardiac disease.

ISSN:0008-4212    

DOI:10.1139/y84-002

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

Using radioligand binding techniques, the effect of reserpine pretreatment on ventricular adrenergic receptors from guinea pig was studied. [3H]Prazosin and [3H]dihydroalprenolol were used to label α1- and β-adrenergic receptors, respectively. Administration of 2.5 mg/kg reserpine for 2 days caused a significant increase in the number of β-adrenergic receptors with no effect on their affinity to respective ligands. Similar reserpine pretreatment did not affect either density or affinity of α1-adrenergic receptors for ligands. The results may explain the previous report from our laboratory in which an identical reserpine pretreatment selectively enhanced the inotropic responsiveness of the working guinea pig heart to isoproterenol.

ISSN:0008-4212    

DOI:10.1139/y84-003

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

To examine the effects of vasopressin on fetal oxygenation the hormone was infused intravenously for 1 h (1.4–3.5 mU∙min−1∙kg fetal weight−1) to chronically catheterized fetal lambs in utero (113–137 days gestation). Arterial pressure rose (48.3 to 59.6 mmHg) (1 mmHg = 133.322 Pa) and heart rate fell (185.3 to 141.0 beats/min) during the infusion. There was a significant increase in fetal arterial(20.0 to 23. 1 mmHg) and significant declines in pH (7.414 to 7.381) and base excess. Umbilical blood flow rose, and the percentage increase in flow (23%) was identical to the proportional rise in arterial pressure. Accompanying the rise in umbilical blood flow was a rise in umbilical oxygen delivery. But as there was no change in fetal oxygen consumption, fractional oxygen extraction by the fetus fell significantly (0.31 to 0.25). These data indicate that the vasopressin-induced rise in fetal vascularresults from an increase in umbilical oxygen delivery and concomitant fall in fractional extraction. Fetal vasopressin levels are greatly elevated during hypoxia, and under conditions of reduced oxygen supply, the effects of the hormone on umbilical oxygen delivery and vascularcould have definite survival va

ISSN:0008-4212    

DOI:10.1139/y84-004

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

The site-specific binding of the potent and selective nucleoside transport inhibitor, [3H]nitrobenzylthioinosine (NBMPR), to the nucleoside transport system of cardiac membranes of several species was investigated. The affinity of [3H]NBMPR for these sites ranged from 0.03 nMin rat to 0.78 nMin dog. The maximal binding capacity of cardiac membranes for [3H]NBMPR was also species dependent and was greatest in bovine and guinea pig heart (2551 and 1700 fmol/mg protein, respectively) and least in rat (195 fmol/mg protein). The affinities of recognized nucleoside transport inhibitors and benzodiazepines for these transport inhibitory sites in guinea pig and rat heart were estimated by studying the inhibition of the site-specific binding of [3H]NBMPR in competition experiments. These values were compared with their inhibitory effects on the transporter-dependent accumulation of [3H]adenosine in guinea pig and rat cardiac muscle segments and with their ability to potentiate the negative inotropic action of adenosine in electrically driven guinea pig and rat left atria. In guinea pig heart, the recognized nucleoside transport inhibitors and benzodiazepines had an order of affinity (dilazep > hydroxynitrobenzylthioguanosine > dipyridamole > hexobendinelidoflazineflunitrazepam > diazepam > lorazepam > flurazepam) for the NBMPR site which was similar to those for the inhibition of [3H]adenosine accumulation and for potentiation of adenosine action. In contrast, in rat heart, where the maximal binding capacity of [3H]NBMPR was lower (eightfold), the nucleoside transporter dependent accumulation of [3H]adenosine was also lower (sixfold) and the negative inotropic action of adenosine was not significantly potentiated. Furthermore, NBMPR sites in rat heart displayed a significantly lower affinity for hexobendine, dipyridamole, and lidoflazine relative to sites in guinea pig hearts. These data indicate that significant differences in cardiac nucleoside transport systems exist among species with respect to both membrane density and drug affinity. Such differences influence the ability of transport inhibitors to modify adenosine action in these tissues.

ISSN:0008-4212    

DOI:10.1139/y84-005

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

Peripheral coronary venous pressures and coronary sinus venous flow were measured in the canine heart as well as intramyocardial, intraventricular, aortic, and coronary artery pressures. Maximum coronary venous flow occurred after maximum intramyocardial and peripheral coronary artery pressures had been reached. Maximum venous flow occurred at or following the maximum peripheral coronary vein pressure. Positive inotropic changes induced by stimulation of the right or left stellate ganglia or infusing isoproterenol, norepinephrine, or dobutamine significantly increased intramyocardial pressure, systolic epicardial coronary venous pressure, and systolic coronary venous flow. Mean coronary sinus flow was augmented by all interventions except isoproterenol. The estimated systolic vein resistance was slightly increased following right stellate ganglion stimulation, but not following left stellate ganglion stimulation, isoproterenol, or dobutamine. Norepinephrine reduced this parameter minimally. These data indicate that coronary veins respond differently to a variety of different positive inotropic interventions.

ISSN:0008-4212    

DOI:10.1139/y84-006

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

In the sartorius of the frog (Rana pipiens), it was found that 10–15% of the tissue sodium was not lost in sodium-free lithium-substituted solution, and was not exchanged with radiosodium in normal frog Ringer's solution, after 4 h. This sodium is not detected by an intracellular sodium-selective glass microelectrode. Detergent or freezing and thawing, in sodium-free solution, cause the loss of all but about 2% of the tissue sodium. The ionophore monensin causes a similar loss but does not disrupt cellular membranes. It was concluded that the slowly exchanging sodium exists in solution inside an organelle whose membrane has a low sodium permeability relative to the sarcolemma, and that this organelle probably is the sarcoplasmic reticulum.

ISSN:0008-4212    

DOI:10.1139/y84-007

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

The reports of early investigators that growth is delayed by thymectomy of immature animals have been confirmed. Although growth is delayed by thymectomy, thymectomized animals approach asymptotically with age the same final weight as corresponding intact animals. Treatment with leucogenenol, a thymothyroid hormone, accelerates the rate of growth of immature neonatally thymectomized rats to that of normal rats. However, treatment with leucogenenol does not increase the rate of growth of normal rats. Treatment with leucogenenol does not change levels of growth hormone (GH) or thyroxine (T4) in the serum of either thymectomized or intact immature and adult rats. Neither is the depression in levels of serum leucogenenol that follows thymectomy associated with a change in serum levels of GH or T4. Thus it is apparent that levels of serum leucogenenol do not affect the rate of growth of immature animals by increasing serum levels of GH or T4. By analogy with the finding that treatment with leucogenenol increases the rate at which committed cells of the bone marrow and cells involved in the immune response develop into functional cells, it is suggested that the levels of serum leucogenenol are one of the factors that determine the rate at which types of body cells that make up bone and other body tissues develop from committed precursors.

ISSN:0008-4212    

DOI:10.1139/y84-008

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

A model is proposed to study the hemodynamics of various types of coronary stenosis. The model coronary artery is assumed to be an elastic tapered tube. A progressive degree of concentric and eccentric stenoses are studied. Measured pulsatile coronary pressure, flow, and intramyocardial pressure are used as input data to calculate the pressure and flow velocities at different locations of the artery. The simulation yields results that agree well with published data in dog experiments, and those from human stenotic coronary arteries. The present model shows that in a cardiac cycle, the overall hydraulic resistance owing to a specific stenosis tends to be flow independent at low flow rate but increases linearly with flow at higher coronary flow. This flow independent resistance increases with progressive stenosis. At low flow, the mean coronary flow in a cardiac cycle is relatively constant with stenoses up to 80%, but decreases dramatically with further increase in the degree of narrowing. At high resting flow rate, this mean flow is markedly reduced at much smaller degrees of constriction. The simulated pressure velocity relation of poststenotic dilatation indicates an additional pressure loss at the distal end of the stenosis, but the calculated resistance to flow is actually lessened. While stenosis length increases pressure loss and resistance to flow, its effect on mean flow appears disproportionally insignificant. Eccentric lesions appear to be more detrimental than concentric ones as they produce additional pressure loss and greater resistance across the coronary artery lesion.

ISSN:0008-4212    

DOI:10.1139/y84-009

出版商:NRC Research Press    

年代:1984

数据来源: NRC

摘要:

The activities of various ammoniagcnic, gluconeogenic, and glycolytic enzymes were measured in the renal cortex and also in the liver of rats made diabetic with streptozotocin. Five groups of animals were studied: normal, normoglycemic diabetic (insulin therapy), hyperglycemic, ketoacidotic, and ammonium chloride treated rats. Glutaminase I, glutamate dehydrogenase, glutamine synthetase, phosphoenolpyruvate carboxykinase (PEPCK), hexokinase, phosphofructokinase, fructose-1,6-diphos-phatase, malate dehydrogenase, malic enzyme, and lactate dehydrogenase were measured. Renal glutaminase I activity rose during ketoacidosis and ammonium chloride acidosis. Glutamate dehydrogenase in the kidney rose only in ammonium chloride treated animals. Glutamine synthetase showed no particular variation. PEPCK rose in diabetic hyperglycemic animals and more so during ketoacidosis and ammonium chloride acidosis. It also rose in the liver of the diabetic animals. Hexokinase activity in the kidney rose in diabetic insulin-treated normoglycemic rats and also during ketoacidosis. The same pattern was observed in the liver of these diabetic rats. Renal and hepatic phosphofructokinase activities were elevated in all groups of experimental animals. Fructose-1,6-diphosphatase and malate dehydrogenase did not vary significantly in the kidney and the liver. Malic enzyme was lower in the kidney and liver of the hyperglycemic diabetic animals and also in the liver of the ketoacidotic rats. Lactate dehydrogenase fell slightly in the liver of diabetic hyperglycemic and NH4Cl acidotic animals. The present study indicates that glutaminase I is associated with the first step of increased renal ammoniagenesis during ketoacidosis. PEPCK activity is influenced both by hyperglycemia and ketoacidosis, acidosis playing an additional role. Insulin appears to prevent renal gluconeogenesis and to favour glycolysis. The latter would seem to remain operative in hyperglycemic and ketoacidotic diabetic animals.

ISSN:0008-4212    

DOI:10.1139/y84-010

出版商:NRC Research Press    

年代:1984

数据来源: NRC