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H Bachelard

Publications and source records attributed to H Bachelard.

At least 19 recordsLinked to original sources
PubMed2001

Effects of insulin on regional blood flow and glucose uptake in Wistar and Sprague-Dawley rats.

The euglycemic-hyperinsulinemic clamp technique in conscious Sprague-Dawley and Wistar rats chronically instrumented with intravascular catheters and pulsed Doppler flow probes was used to examine insulin's actions on regional blood flow and glucose metabolism. The effect of insulin on in vivo and in vitro glucose utilization in individual muscles was estimated using [3H]-2-deoxy-D-glucose. We found that in both strains, insulin (4, 32, and 64 mU x kg(-1) x min(-1)) causes similar cardiovascular changes characterized by slight increases in blood pressure (at high dose), vasodilation in renal and hindquarter vascular beds, and vasoconstriction (at high dose) in the superior mesenteric vascular bed. However, at the lowest dose of insulin tested, we found a smaller insulin sensitivity index and a lower insulin-stimulated in vivo glucose uptake in extensor digitorum longus (EDL) muscles of Wistar versus Sprague-Dawley rats. Higher insulin-stimulated glucose transport activity was found in isolated soleus muscle, while greater basal glucose transport was noted in isolated EDL muscle from Sprague-Dawley versus Wistar rats. These results provide further evidence for an insulin blood flow-regulatory effect and suggest that strain characteristics (differences in muscle perfusion, hindquarter composition, or fiber insulin sensitivity) constitute a major determinant in the variation in whole-body insulin sensitivity.

Animals↗
PubMed2000

Effect of metformin on the vascular and glucose metabolic actions of insulin in hypertensive rats.

We investigated the long-term effect of metformin treatment on blood pressure, insulin sensitivity, and vascular responses to insulin in conscious spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and blood flow. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Two groups of SHR received metformin (100 or 300 mg x kg(-1) x day(-1)) for 3 wk while another group of SHR and a group of Wistar Kyoto (WKY) rats were left untreated. We found that vasodilation of skeletal muscle and renal vasculatures by insulin is impaired in SHR. Moreover, a reduced insulin sensitivity was detected in vivo and in vitro in isolated soleus and extensor digitorum longus muscles from SHR compared with WKY rats. Three weeks of treatment with metformin improves the whole-body insulin-mediated glucose disposal in SHR but has no blood pressure-lowering effect and no influence on vascular responses to insulin (4 mU x kg(-1) x min(-1)). An improvement in insulin-mediated glucose transport activity was detected in isolated muscles from metformin-treated SHR, but in the absence of insulin no changes in basal glucose transport activity were observed. It is suggested that part of the beneficial effect of metformin on insulin resistance results from a potentiation of the hormone-stimulating effect on glucose transport in peripheral tissues (mainly skeletal muscle). The results argue against a significant antihypertensive or vascular effect of metformin in SHR.

Animals↗
PubMed1999

Isradipine and insulin sensitivity in hypertensive rats.

The present study was designed to investigate the effect of a reduction in blood pressure, by using the calcium channel antagonist isradipine, on insulin sensitivity and vascular responses to insulin in conscious spontaneously hypertensive male rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique. Two groups of rats received isradipine at a dose of 0.05 or 0.15 mg. kg-1. h-1, whereas a third group received a continuous infusion of vehicle (15% DMSO). Both doses of isradipine were found to decrease mean blood pressure (-25 +/- 4 mmHg at the dose of 0.05 mg. kg-1. h-1 and -20 +/- 2 mmHg at the dose of 0.15 mg. kg-1. h-1) and to improve insulin sensitivity. Moreover, in the rats treated with the low dose of isradipine, we observed vasodilations in renal, superior mesenteric, and hindquarter vascular beds. In the untreated group, the euglycemic infusion of insulin (4 mU. kg-1. min-1) was found to cause vasoconstrictions in superior mesenteric and hindquarter vascular beds, but no changes in mean blood pressure, heart rate, or renal vascular conductance were found. In contrast, in the isradipine-treated groups, the same dose of insulin was found to produce vasodilations in the renal vascular bed and to abolish the vasoconstrictor responses previously observed. We concluded that short-term treatment with isradipine in SHR can lower blood pressure and improve insulin sensitivity, mainly through hemodynamic factors, as supported by experiments with hydralazine as a positive vasodilator control.

Animals↗
PubMed1999

Incommensurate frequencies of major vascular regulatory mechanisms.

The dynamic relationship among three major vascular control mechanisms that operate on large fractions of cardiac output: arterial baroreflex and renal and mesenteric autoregulation, was investigated in conscious rats. Wistar and spontaneously hypertensive rats were studied in their home cages 10 days after implantation of pulsed Doppler flow probes. There was an oscillation of blood pressure centered at 0.45 Hz that is associated with operation of arterial baroreflexes. Hindquarters blood flow displayed a featureless, "1/f' power spectrum, in which no autoregulatory or baroreflex signatures could be discerned, although active control of resistance over a wide range of frequencies was evident. The renal pressure - flow transfer function was dominated by an autoregulatory mechanism with a resonance peak at 0.25 +/- 0.01 Hz. In the mesenteric circulation an autoregulatory mechanism was seen with a resonance peak at 0.15 +/- 0.01 Hz and another active mechanism was seen above 0.2 Hz that appeared from its negative admittance phase to be a baroreflex. The center frequencies of mesenteric and renal autoregulation and of the arterial baroreflex were related in a ratio of 1 : 1.7 +/- 0.1 : 3.0 +/- 0.2 (approximately 4:7:12). Such relatively high order ratios can be expected to minimize the possibility of phase locking and (or) entrainment among the various control mechanisms.

Animals↗
PubMed1998

Responses of mesenteric and renal blood flow dynamics to acute denervation in anesthetized rats.

Previous studies have shown that renal autoregulation dynamically stabilizes renal blood flow (RBF). The role of renal nerves, particularly of a baroreflex component, in dynamic regulation of RBF remains unclear. The relative roles of autoregulation and mesenteric nerves in dynamic regulation of blood flow in the superior mesenteric artery (MBF) are similarly unclear. In this study, transfer function analysis was used to identify autoregulatory and baroreflex components in the dynamic regulation of RBF and MBF in Wistar rats and young spontaneously hypertensive rats (SHR) anesthetized with isoflurane or halothane. Wistar rats showed effective dynamic autoregulation of both MBF and RBF, as did SHR. Autoregulation was faster in the kidney (0.22 +/- 0.01 Hz) than in the gut (0.13 +/- 0.01 Hz). In the mesenteric, but not the renal bed, the admittance phase was significantly negative between 0.25 and 0. 7 Hz, and the negative phase was abrogated by mesenteric denervation, indicating the presence of an arterial baroreflex. The baroreflex was faster than autoregulation in either bed. The presence of sympathetic effects unrelated to blood pressure was inferred in both vascular beds and appeared to be stronger in the SHR than in the Wistar rats. It is concluded that a physiologically significant baroreflex operates on the mesenteric, but not the renal circulation and that blood flow in both beds is effectively stabilized by autoregulation.

Animals↗
PubMed1998

Landmarks in the application of 13C-magnetic resonance spectroscopy to studies of neuronal/glial relationships.

The development of the use of carbon isotopes as metabolic tracers is briefly described. 13C-labelled precursors (13CO2, 13CH4) first became available in 1940 and were studied in microorganisms, but their use was limited by very low enrichments and lack of suitable analytical equipment. More success was achieved with 11C and especially 14C, as these radioactive tracers did not need to be highly enriched. Although the stable 13C isotope can be used at a low percentage enrichment in mass spectrometry, its application to magnetic resonance spectroscopy (MRS) requires very highly enriched precursors, due to its low natural abundance and low sensitivity. Despite such limitations, however, the great advantage of 13C-MRS lies in its exquisite chemical specificity, in that labelling of different carbon atoms can be distinguished within the same molecule. Effective exploitation became feasible in the early 1970s with the advent of stable instruments, Fourier transform 13C-MRS, and the availability of highly enriched precursors. Reports of its use in brain research began to appear in the mid-1980s. The applications of 13C isotopomer analysis to research on neuronal/glial relationships are reviewed. The presence of neighbouring 13C-labelled atoms affects the appearance of the resonances (splitting due to C-C coupling), and so allows for unique quantification of rates through different and possibly competing pathways. Isotopomer patterns in resonances labelled from a combination of [1-13C]glucose and [1, 2-13C2]acetate have revealed aspects of neuronal/glial metabolic trafficking on depolarization and under hypoxic conditions in vitro. This approach has now been applied to in vivo studies on inhibition of glial metabolism using fluoroacetate. The results confirm the glial specificity of the toxin and demonstrate that it does not affect entry of acetate. When the glial TCA cycle is inhibited, the ability of the glia to participate in the glutamate/glutamine cycle remains unimpaired, in that labelling of glutamine, which can only be derived from neuronal metabolism of glucose, persists. The results also confirmed earlier evidence that part of the GABA transmitter pool is derived from glial glutamine.

Acetates↗
PubMed1997

Trafficking of amino acids between neurons and glia in vivo. Effects of inhibition of glial metabolism by fluoroacetate.

Glial-neuronal interchange of amino acids was studied by 13C nuclear magnetic resonance spectroscopy of brain extracts from fluoroacetate-treated mice that received [1,2-(13)C]acetate and [1-(13)C]glucose simultaneously. [13C]Acetate was found to be a specific marker for glial metabolism even with the large doses necessary for nuclear magnetic resonance spectroscopy. Fluoroacetate, 100 mg/kg, blocked the glial, but not the neuronal tricarboxylic acid cycles as seen from the 13C labeling of glutamine, glutamate, and gamma-aminobutyric acid. Glutamine, but not citrate, was the only glial metabolite that could account for the transfer of 13C from glia to neurons. Massive glial uptake of transmitter glutamate was indicated by the labeling of glutamine from [1-(13)C]glucose in fluoroacetate-treated mice. The C-3/C-4 enrichment ratio, which indicates the degree of cycling of label, was higher in glutamine than in glutamate in the presence of fluoroacetate, suggesting that transmitter glutamate (which was converted to glutamine after release) is associated with a tricarboxylic acid cycle that turns more rapidly than the overall cerebral tricarboxylic acid cycle.

Acetates↗
PubMed1997

Mechanisms of the regional hemodynamic effects of a mu-opioid receptor agonist microinjected into the hypothalamic paraventricular nuclei of conscious unrestrained rats.

The present study was undertaken to characterize the mechanisms of the hemodynamic responses to microinjection of the selective mu-opioid receptor agonist [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO) into the paraventricular nucleus of the hypothalamus, in conscious rats chronically instrumented with pulsed Doppler flow probes. We found that i.v. pretreatment with phentolamine had no effect on the tachycardia elicited by DAMGO (1 nmol); however, the pressor response was reversed to a state of hypotension, the renal and superior mesenteric vasoconstrictions were attenuated and the hindquarter vasodilation was potentiated. In the presence of propranolol, the pressor response and renal vasoconstriction were unchanged, whereas the superior mesenteric vasoconstriction was reduced and the hindquarter vasodilation was abolished. Moreover, in those animals we observed bradycardia followed by tachycardia. Combined i.v. pretreatment with phentolamine and propranolol abolished the pressor and heart rate responses to DAMGO but had no effect on the renal and superior mesenteric vasoconstrictions, although the hindquarter vasodilation was reduced. Intravenous pretreatment with a vasopressin V1 receptor antagonist or captopril had no effect on the cardiovascular responses to DAMGO. Together, these results indicate that the hypertension observed after injection of DAMGO into the paraventricular nucleus of the hypothalamus was secondary to alpha adrenoceptor-mediated vasoconstrictions in renal and superior mesenteric vascular beds and to beta adrenoceptor-mediated vasodilation in the hindquarter vascular bed, whereas the involvement of circulating vasopressin or angiotensin seems less obvious from the present findings. However, we cannot exclude the possibility that nonadrenergic, nonvasopressinergic and nonangiotensinergic vasoconstrictor mechanisms were acting in the renal and superior mesenteric vascular beds.

Animals↗
PubMed1996

Insulin sensitivity and hemodynamic responses to insulin in Wistar-Kyoto and spontaneously hypertensive rats.

The insulin-mediated vasodilator effect has been proposed as an important physiological determinant of insulin action on glucose disposal in normotensive humans. The present study was designed to further examine the acute regional hemodynamic effects of insulin in different vascular beds and to explore the relationships between insulin vascular effects and insulin sensitivity during euglycemic hyperinsulinemic clamps in conscious normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and regional blood flows. In WKY rats, the euglycemic infusion of insulin (4 and 16 mU.kg-1.min-1) causes vasodilations in renal and hindquarter vascular beds but no changes in mean blood pressure, heart rate, or superior mesenteric vascular conductance. In contrast, in SHR, the same doses of insulin produce vasoconstrictions in superior mesenteric and hindquarter vascular beds and, at high doses, increase blood pressure. Moreover, at the lower dose of insulin tested, we found a reduction in the insulin sensitivity index in the SHR compared with the WKY rats. The present findings provide further evidence for an association between insulin sensitivity and insulin-mediated hemodynamic responses.

Animals↗
PubMed1996

Approaches to studies on neuronal/glial relationships by 13C-MRS analysis.

The use of different 13C-labelled precursors alone or in combination ([1-13C]glucose, [2-13C]glucose, [1-13C]acetate, [2-13C]acetate and [1,2-13C2]acetate) to study neuronal/glial metabolic relationships by MRS is discussed. Glutamine and citrate resonances represent glial metabolism if a combination of [1-13C]glucose + [2-13C]acetate is used, but only for short time periods. A combination of [2-13C]glucose + [2-13C]acetate will label -COO- groups from glucose and -CH2 groups from acetate, respectively, which distinguish well in theory. However, this approach is severely limited by the long T1S of -COO- groups and low S/N. Contributions of the anaplerotic pathway can be assessed using [2-13C]glucose, but again can be limited by the long T1S of -COO- groups. Labelling of glycerol-3-phosphate (believed to be produced in glia) from [1-13C]glucose is difficult to see under normal conditions but has proved useful in, e.g., hypoxia. We believe the most promising approach is the use of [1-13C] glucose with [1,2-13C2]acetate, by analysis of the multiplets ('isotopomers') of the amino acid resonances.

Acetates↗
PubMed1995

High-field MRS studies in brain slices.

We are applying multi-nuclear high-field (500 MHz) MR spectroscopy of metabolising whole tissue preparations of the mammalian brain to studies on individual components of convulsions, which include prolonged depolarization, metabolic deprivation, and the effects of excitotoxins. The responses of glial cells and neurones can be partially distinguished by following labelling patterns of metabolic intermediates from 13C-labelled glucose or acetate (which enters only glial cells). This approach clearly confirmed our earlier indications that the metabolic response to depolarization (40 mM extracellular K+) occurs essentially in glial cells. Some evidence for metabolic shuttling between glia and neurones was obtained from the changes in C3/C4 ratios of glutamate and glutamine, and the C2/C3 of GABA. Mechanisms for metabolic support of neurones by glia may be of importance in neuronal protection under such metabolic stress as occurs in epilepsy. Changes in free intracellular divalent cations ([Ca2+]i and [Zn2+]i) were monitored using the 19F-MRS indicator, 5FBAPTA. Large increases in [Ca2+]i and decreases in PCr were produced by excitotoxins (glutamate and NMDA), depolarization or ischemia, but intracellular Zn2+ appeared only after exposure to the excitotoxins. The NMDA receptor blocker, MK801, removed all of the responses to NMDA, but only prevented the appearance of Zn2+ observed with glutamate. These results indicate that the damage caused to neurones by such insults as convulsions is not due simply to the presence of excessive excitotoxic glutamate.

Animals↗
PubMed1995

Regional haemodynamic effects of mu-, delta-, and kappa-opioid agonists microinjected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats.

1. The cardiovascular effects of bilateral injection into the hypothalamic paraventricular nuclei of selective mu-, delta-, and kappa-opioid receptor agonists were investigated in conscious, unrestrained Wistar Kyoto rats, chronically instrumented with pulsed Doppler flow probes for measurement of regional haemodynamics. 2. The selective mu-agonist [D-Ala2,MePhe4,Gly5ol]enkephalin (DAMGO), injected bilaterally into the hypothalamic paraventricular nuclei (0.01-1.0 nmol), caused increases in blood pressure, tachycardias, vasoconstriction in renal and superior mesenteric vascular beds and substantial vasodilatation in the hindquarter vascular bed. 3. The administration of increasing doses (0.01-5.0 nmol) of the selective delta-agonist [D-Phe2,5]enkephalin (DPDPE) or the selective kappa-agonist, U50488H into the paraventricular nuclei (PVN) had no significant effect on blood pressure, heart rate, or regional haemodynamics. 4. Together, the present results are further evidence of a role for opioid peptides, especially acting at mu-receptors in the PVN, in the central regulation of the cardiovascular system, whereas a role for opioid peptides, acting at delta- and kappa-receptors in the PVN, seems less obvious from the present results.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1994

Regional haemodynamic effects of carbachol injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats.

Carbachol was injected into the hypothalamic paraventricular nuclei (PVN) of conscious, unrestrained Long Evans rats, chronically instrumented with intravascular catheters and pulsed Doppler probes to assess changes in regional haemodynamics. Bilateral microinjections of carbachol (1 ng-1 microgram) produced increases in blood pressure, bradycardias and vasoconstrictions in renal, superior mesenteric and hindquarters vascular beds. In the presence of phentolamine, the bradycardic and hindquarters vasoconstrictor responses to carbachol were unchanged while the pressor response was smaller due to a reduction in the renal and the superior mesenteric vasoconstriction. In the presence of propranolol, the bradycardic response was reduced, but the pressor and renal vasoconstrictor responses were potentiated, whereas the superior mesenteric and hindquarter vasoconstrictions were not changed significantly. In the presence of phentolamine and propranolol, the heart rate and pressor responses, as well as the renal vasoconstriction, were unchanged, whereas the superior mesenteric vasoconstriction was reduced and the hindquarters vasoconstriction was potentiated. Together these results are consistent with an involvement of the sympathoadrenal system in the pressor response to carbachol injected into the PVN of untreated animals. They indicate that alpha-adrenoceptor-mediated vasoconstriction in the superior mesenteric vascular bed is a particularly important component in that regard. In the presence of the vasopressin antagonist, d(CH2)5(Tyr(Et))DAVP, alone or in combination with phentolamine and propranolol, the pressor response to carbachol was substantially reduced, while the renal and superior mesenteric vasoconstrictor effects were completely abolished; the bradycardia was not significantly affected by this treatment. These results indicate an important involvement of vasopressin in the cardiovascular responses to carbachol injected into the PVN of untreated animals. Moreover, in the presence of the vasopressin antagonist the hindquarters vascular bed showed a vasodilatation following PVN injection of carbachol; this effect was reversed to a vasoconstriction following combined i.v. pretreatment with the vasopressin antagonist, phentolamine and propranolol and hence was possibly due to circulating adrenaline acting on vasodilator beta 2-adrenoceptors. However, there was a residual hindquarters vasoconstriction raising the possibility that non-adrenergic, non-vasopressinergic vasoconstrictor mechanisms were influencing that vascular bed.

Adrenergic alpha-Antagonists↗
PubMed1994

Excitotoxic amino acids cause appearance of magnetic resonance spectroscopy-observable zinc in superfused cortical slices.

(1) The effects of glutamate and NMDA on the free intracellular calcium concentration ([Ca2+]i) have been followed in superfused cortical slices using the 19F-magnetic resonance indicator 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA). (2) Glutamate (0.5 or 1 mM) caused a 75-100% increase in [Ca2+]i, and a new resonance was attributed to zinc-5FBAPTA, which was confirmed from its disappearance in the presence of a high-affinity chelator of heavy metals, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine. The appearance of zinc occurred with or just after the rise in [Ca2+]i and was independent of Mg2+. (3) NMDA, N-methyl-DL-aspartate, or N-methyl-L-aspartate (10-200 microM) caused a slower increase in [Ca2+]i, and zinc was observed in some but not all experiments. When present, zinc appeared later than the increase in [Ca2+]i. These changes were also independent of Mg2+. (4) Decreases in both phosphocreatine and ATP were observed in all of these studies. (5) The results are discussed in terms of the proposed role of zinc as a modulator of excitotoxicity. Observations of zinc after exposure to glutamate or more slowly to NMDA, but not after depolarisation or deprivation of glucose and O2 (where increases also occur in [Ca2+]i), suggest that the cellular damage caused by the latter insults (depolarisation and fuel deprivation as in ischaemia) involves mechanisms not solely attributable to release of excitotoxins.

Animals↗
PubMed1993

Cardiovascular effects of neuronal activation of the extended amygdala in rats.

The bed nucleus of the stria terminalis (BST) and the sublenticular substantia innominata (SI) are considered rostral extensions of the medical and central amygdaloid nuclei. In contrast to amygdaloid nuclei proper, the involvement of BST and SI neurons in cardiovascular control has not been studied. These areas were systematically explored in 35 urethane-anesthetized Wistar rats for sites from which changes in arterial pressure (AP) and heart rate (HR) could be obtained by injection of 20 nl of glutamate solutions (Glu, 0.5 M). Injections into 84 of the 130 histologically verified sites were followed after an 8.0 +/- 0.7 s latency by depressor responses ranging from -4 to -33 (mean -13.3 +/- 0.8) mmHg, accompanied by variable changes in HR. Pressor responses were elicited from only 3 sites; 43 sites were not responsive. An additional group of 10 rats was instrumented for bilateral Glu injections (0.1 M, 200 nl per side) into the ventral division of the lateral BST and ventral BST and for the recording of AP, HR and regional blood flows measured with pulsed Doppler probes in the conscious state. In these rats, decreases in AP (-11.9 +/- 1.7 mmHg) were accompanied by significant increases in hindquarter conductance (44.2 +/- 11.4%), while renal and mesenteric vascular conductances remained unchanged. The fall in AP usually preceded the rise in hindquarter flow. These results suggest the existence of a depressor area in regions of the BST and SI, but the contribution of the elicited depressor effects in the overall central control of the circulation remains to be established.

Amygdala↗