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Biomedical subjects

H Bachelard

Publications and source records attributed to H Bachelard.

35 records · Page 2Linked to original sources
PubMed1993

Studies on metabolic regulation using NMR spectroscopy.

The effects of hypoxia and hypoglycaemia on cerebral metabolism and calcium have been studied using multinuclear magnetic resonance spectroscopy. 13C MRS showed that severe hypoxia did not cause any further increase in metabolic flux into lactate seen in mild hypoxia, but there was a further increase in 13C labelling of alanine and glycerol 3-phosphate. These results are discussed in terms of the ability of lactate dehydrogenase to maintain normal levels of NADH in mild hypoxia, but not in severe hypoxia. We conclude that glycerol 3-phosphate and alanine may provide novel means of monitoring severe hypoxia whereas lactate is a reliable indicator only of mild hypoxia. 19F- and 31P NMR spectroscopy showed that neither hypoxia nor hypoglycaemia alone caused any significant change in [Ca2+]i. Combined sequential insults (hypoxia, followed by hypoxia plus hypoglycaemia), or vice versa, produced a 100% increase in [Ca2+]i, whereas immediate exposure to the combined insult (hypoxia plus hypoglycaemia) resulted in a large 5-fold increase in [Ca2+]i, with severe irreversible effects on the energy state. These results are discussed in terms of metabolic adaptation to the single type of insult, which renders the tissue less vulnerable to the combined insult. The effects of this combined insult are far more severe than those caused by glutamate or NMDA, which throws doubt on the current excitoxic hypothesis of cell damage.

Animals↗
PubMed1992

Regional haemodynamic effects of noradrenaline injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats: possible mechanisms of action.

The cardiovascular effects of noradrenaline bilaterally injected into the hypothalamic paraventricular nuclei were investigated in conscious, unrestrained Long-Evans rats and homozygous, vasopressin-deficient Brattleboro rats, chronically instrumented with pulsed Doppler probes for measurement of regional haemodynamics. In Long-Evans rats, incremental doses of noradrenaline (0.01-10 nmol) caused dose-related increases in blood pressure and a substantial, dose-related, superior mesenteric vasoconstriction. These changes were accompanied by bradycardia and reductions in renal and hind-quarter vascular conductances. In Brattleboro rats, noradrenaline (10 nmol) had no effect on blood pressure, heart rate, or renal or superior mesenteric vascular conductances. However, there was a slight vasodilatation in the vascular bed of the hindquarters. In Long-Evans rats, intravenous pretreatment with phentolamine had no effect on the bradycardia but partly inhibited the pressor response to noradrenaline injected into the paraventricular nuclei. These effects were associated with a smaller superior mesenteric vasoconstriction and an abolition of the vasoconstriction in the hindquarters. Combined intravenous pretreatment with phentolamine and propranolol had no effect on the heart rate or pressor responses to noradrenaline injected into the paraventricular nuclei, but reduced the superior mesenteric vasoconstriction, potentiated the vasoconstriction in the hindquarters and eliminated the renal vasoconstriction. These results suggest that, in untreated Long-Evans rats, alpha-adrenoceptor-mediated constriction in the mesenteric vascular bed and beta-adrenoceptor-mediated dilatation in the vascular bed of the hindquarters have important influences on the pressor response to noradrenaline injected into the paraventricular nuclei. In the presence of the vasopressin V1-receptor antagonist, d(CH2)5[Tyr(Et)]DAVP, the pressor and heart rate responses to noradrenaline injected into the paraventricular nuclei were abolished, as were the vasoconstrictions in the renal, superior mesenteric and hindquarter vascular beds. Together these results suggest an interaction between the sympathoadrenal system and vasopressin-mediated mechanisms in the cardiovascular responses to noradrenaline injected bilaterally into the paraventricular nuclei of conscious, untreated rats.

Animals↗
PubMed1992

Mechanisms contributing to the regional haemodynamic effects of neurotensin in conscious, unrestrained Long Evans rats.

1. The regional haemodynamic effects of i.v. bolus doses of neurotensin (10-1000 ng) were assessed in conscious, unrestrained Long Evans rats chronically instrumented with miniaturized, pulsed Doppler probes. 2. Neurotensin caused increases in blood pressure, together with dose-related tachycardias and constrictions in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia elicited by the 1000 ng dose of neurotensin was preceded by a transient bradycardia. 3. In the presence of phentolamine, the pressor effect of neurotensin (1000 ng) was converted into a hypotensive effect, accompanied by reduced tachycardic and constrictor responses in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia was not preceded by a bradycardia. 4. In the presence of phentolamine and propranolol, the pressor and bradycardic responses to neurotensin were unaffected, whereas the tachycardia was abolished. The renal vasconstrictor effect was smaller, while the constrictions in the superior mesenteric and hindquarters vascular beds were not different from those in untreated rats. 5. In rats neonatally treated with capsaicin (50 mg kg-1, s.c.), the pressor effects elicited by neurotensin (300 and 1000 ng) were reduced as were the constrictor responses in the renal (at the dose of 300 ng), superior mesenteric (at the dose of 300 ng) and hindquarters (at both doses) vascular beds. The bradycardia elicited by neurotensin (1000 ng) was absent, whereas the tachycardia was potentiated. 6. The results indicate that in conscious, intact rats neurotensin appears to exert cardiovascular influences through activation of sympathoadrenal mechanisms and also through non-adrenergic effects on the heart, renal, superior mesenteric and hindquarters vascular beds. The latter effects appear to involve capsaicin-sensitive nerves.

Animals↗
PubMed1992

Involvement of capsaicin-sensitive neurones in the haemodynamic effects of exogenous vasoactive peptides: studies in conscious, adult Long Evans rats treated neonatally with capsaicin.

1. The regional haemodynamic effects of i.v. bolus injections of bradykinin (0.05 or 0.5 nmol), cholecystokinin (0.175 or 1.75 nmol), substance P (0.01 or 0.1 nmol) and calcitonin gene-related peptide (0.05 or 0.5 nmol) were assessed in conscious, adult Long Evans rats that had been treated neonatally with either capsaicin (50 mg kg-1, s.c.) or vehicle. 2. In vehicle-treated rats, both doses of bradykinin were without effect on blood pressure, but caused tachycardia and hindquarters vasodilatation. Moreover, after the higher dose there were dilatations in the renal and superior mesenteric vascular beds. In capsaicin-treated rats the hindquarters vasodilator effects elicited by both doses of bradykinin were significantly reduced, while the tachycardia and responses in the renal and superior mesenteric vascular beds were unchanged. 3. In vehicle-treated rats, cholecystokinin caused dose-dependent increases in blood pressure accompanied by renal, superior mesenteric and hindquarters vasoconstriction followed, after the higher dose, by a hindquarters vasodilatation. The lower dose produced a tachycardia, while there was a bradycardia followed by a tachycardia after the higher dose. In capsaicin-treated rats, the pressor response, as well as the renal vasoconstrictor effects of cholecystokinin, were greater than in vehicle-treated rats, while the heart rate, superior mesenteric or hindquarters responses were not different. 4. In vehicle-treated rats, substance P produced a dose-dependent depressor response and tachycardia accompanied by dilatations in the renal and hindquarters vascular beds and constriction in the superior mesenteric vascular bed. In capsaicin-treated rats, the responses to the lower dose of substance P were not different from those in vehicle-treated rats, while the depressor response to the higher dose of substance P was slightly less than in vehicle-treated rats and the renal vasodilatation was absent.5. In vehicle-treated rats, calcitonin gene-related peptide caused dose-dependent hypotensive and tachycardic effects associated with dilatations in renal and hindquarters vascular beds and a constriction in the superior mesenteric vascular bed. After the higher dose, the renal vasodilatation was followed by a modest vasoconstriction. In capsaicin-treated rats, the depressor responses to both doses of calcitonin generelated peptide were slightly more prolonged than in vehicle-treated animals, whereas the heart rate and renal and mesenteric vascular conductance changes were not significantly different. However, there was a more sustained hindquarters vasodilator response to the higher dose of calcitonin gene-related peptide in the capsaicin-treated rats.6. The results suggest that peripheral, capsaicin-sensitive neurones are involved in the cardiovascular responses to exogenous bradykinin and cholecystokinin in conscious rats. It does not appear that the extent of involvement of these neurones is underestimated on account of development of marked supersensitivity to the peptides they normally release, since responses to such peptides (e.g. substance P and calcitonin gene-related peptide) are relatively normal in capsaicin-treated rats.

Analysis of Variance↗
PubMed1991

Posterior hypothalamic receptors involved in the cardiovascular changes elicited by electrical stimulation of the rostral ventrolateral medulla.

The posterior hypothalamic receptors involved in the cardiovascular responses to electrical stimulation of the rostral ventrolateral medulla were investigated in urethane-anaesthetized rats. Electrical stimulation of the rostral ventrolateral medulla produced a significant increase in systolic blood pressure. This response was significantly attenuated by the prior administration of d,l-propranolol (20 micrograms), clonidine (8 micrograms), atropine (8 micrograms) or methysergide (10 micrograms) into the posterior hypothalamus, but not by cimetidine (11 micrograms), chlorpheniramine (12 micrograms), naloxone (10 micrograms) or a vasopressin V1 antagonist (100 ng). The effect of clonidine (8 micrograms) on the pressor response to stimulation of the rostral ventrolateral medulla was antagonized by idazoxan (66 micrograms). These results confirm that the cardiovascular changes elicited by stimulation of the rostral ventrolateral medulla area are, in part, centrally modulated by alpha 2 and beta-adrenoceptors in the posterior hypothalamus which exert respectively, inhibitory and stimulatory effect. Furthermore the results indicate the involvement of posterior hypothalamic cholinergic and serotonergic receptors in the pressor response produced by stimulation of the rostral ventrolateral medulla.

Adrenergic alpha-Antagonists↗
PubMed1990

Cardiovascular responses elicited by chemical stimulation of the rostral ventrolateral medulla in conscious, unrestrained rats.

The cardiovascular effects of microinjection of L-glutamic acid into the rostral ventrolateral medulla have been investigated in anaesthetized and in conscious, unrestrained rats. In conscious rats L-glutamic acid (0.36, 1.2 and 2.4 nmol) produced significant increases in blood pressure, generally accompanied by a bradycardia. A lower dose of L-glutamic acid (0.12 nmol) had no effect on blood pressure or heart rate. The cardiovascular responses elicited by L-glutamic acid (2.4 nmol) were completely abolished by intravenous infusion of the ganglion blocker, pentolinium. However, in urethane-anaesthetized rats, the pressor response (+27 +/- 2/+21 +/- 2 mmHg) to microinjection of L-glutamic acid (2.4 nmol) was markedly less than that seen in conscious rats (+64 +/- 6/+47 +/- 3 mmHg) and there was a tachycardia (+21 +/- 2 beats/min) rather than a bradycardia. These results corroborate previous studies, carried out in anaesthetized animals, indicating that stimulation of the rostral ventrolateral medulla provides direct and/or indirect excitatory drive to the preganglionic sympathetic neurons of the spinal cord to increase blood pressure, but demonstrate a marked difference in sensitivity in conscious vs urethane-anaesthetized animals.

Animals↗
PubMed1987

Epicardial application of capsaicin causes tachycardia and pressor effect in guinea pigs.

Topical application of picomoles of capsaicin (CAP) to the surface of the left ventricle (epicardial application) of anesthetized guinea pigs evoked dose-dependent increases of heart rate and of mean arterial blood pressure. The pressor responses to epicardial application of CAP were inhibited by systemic administration of pentolinium or a mixture of phentolamine and propranolol whereas only the mixture of phentolamine and propranolol attenuated the tachycardia. The pressor and heart rate responses to epicardial CAP were not modified by acute bilateral vagotomy or prior systemic treatment of animals with atropine, indomethacin, naloxone or a mixture of mepyramine and cimetidine, but both responses were markedly reduced by prior chronic treatment of guinea pigs with CAP or by prior epicardial application of lidocaine. Altogether these results suggest that the pressor effects caused by epicardial application of CAP in anesthetized guinea pigs are reflex in nature and likely to be due to stimulation by CAP of cardiac, sympathetic, CAP-sensitive, sensory nerve endings, whereas the tachycardia caused by epicardial CAP might be mediated by local noradrenaline release (and subsequent cardiac beta adrenoceptor activation) from cardiac, sympathetic, postganglionic nerve fibers and/or terminals.

Administration, Topical↗
PubMed1984

The contractile effect of bombesin, gastrin releasing peptide and various fragments in the rat stomach strip.

The contractile activity of bombesin (BB) and related peptides including the gastrin releasing peptide (GRP) was evaluated in the rat stomach strip. BB and GRP were found to elicit concentration-dependent contractile effects in concentrations varying between 5.0 X 10(-10) and 5.0 X 10(-7) M. EC50 values of BB and GRP were 6.5 X 10(-9) and 10(-8) M, respectively. The contractile effect of BB (1.5 X 10(-8) M) was not modified by a mixture of antagonists containing atropine (1.7 X 10(-6) M), mepyramine (1.2 X 10(-6) M), methysergide (1.4 X 10(-6) M), phentolamine (1.8 X 10(-6) M), propranolol (1.9 X 10(-6) M) and indomethacin (7.0 X 10(-6) M), nor by the nerve paralyzing drug tetrodotoxin (1.6 X 10(-6) M). These results suggest the existence of BB receptors in the rat stomach strip. The results also suggest that the contractile effects of BB in this tissue result from a direct effect on the smooth muscle cell. The data derived from our structure-activity study indicate that deletion of the N-terminal sequence pGlu1-Gln2-Arg3-Leu4-Gly5- from the BB molecule causes practically no loss of affinity and intrinsic activity. Further shortening of BB gives rise to a gradual reduction of both parameters. Residual contractile activity could still be observed with the tetra- and pentapeptide BB-(11-14) and BB-(10-14) at 10(-5) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The chronotropic action of neurotensin in the guinea pig isolated heart.

Neurotensin (NT) infusions into isolated, perfused, spontaneously beating hearts of guinea pigs evoked a concentration-dependent, positive chronotropic effect which was preceded in some hearts by transient bradycardia. The tachycardia caused by NT was not affected by propranolol, cimetidine, indomethacin, a mixture of methysergide and morphine or by atria removal. The incidence and amplitude of bradycardia caused by NT were increased by neostigmine but reduced by atropine. Neostigmine and atropine also tended to decrease and increase respectively, the tachycardia caused by NT. These results suggest that the positive chronotropic effect of NT in guinea pig isolated heart results from a direct effect on the specialized conduction system of the heart while its negative chronotropic effect is likely to reflect the activation by NT of cardiac vagal cholinergic neurons.

Animals↗
PubMedDate not supplied

The coronary vasodilator effect of neurotensin in the guinea pig isolated heart.

Neurotensin (NT) infusions into isolated, electrically-driven hearts of guinea pigs, elicited concentration-dependent reductions of myocardial perfusion pressure accompanied by proportional increases of myocardial tension. The decrease of myocardial perfusion pressure caused by NT (attributed to the coronary vasodilator effect of NT) was highly dependent on basal (pre-NT infusions) levels of perfusion pressure, being larger at high perfusion pressure (e.g., 75 mmHg) values than at lower ones (e.g., 50 and 25 mmHg). The perfusion pressure-lowering effect on NT was potentiated and inhibited by neostigmine and atropine, respectively. It was slightly inhibited by methysergide. However, it was not affected by propranolol, indomethacin or a mixture of diphenhydramine and cimetidine. The decreases of myocardial perfusion pressure caused by NT were abolished by NT receptor desensitization, while those evoked by acetylcholine or vasoactive intestinal peptide (VIP) were minimally affected by the desensitization. These results indicate that NT exerts a vasodilator effect in guinea pig coronary vessels. This effect is likely to involve the participation of acetylcholine released from NT-stimulated cardiac cholinergic (vagal) neurons and/or nerve terminals and to be mediated by specific NT receptors. The possible contribution of intracardiac serotonin and/or its receptors to the coronary vasodilator effect of NT is discussed.

Animals↗
PubMedDate not supplied

The vasoconstrictor effect of neuropeptide Y and related peptides in the guinea pig isolated heart.

Neuropeptide Y (NPY) infusions into isolated, perfused, spontaneously beating hearts of guinea pigs elicited concentration-dependent increases of myocardial perfusion pressure and decreases of myocardial tension, but no consistent changes of heart rate. The increase of perfusion pressure caused by NPY (attributed to a constrictor effect on coronary vessels) was not affected by atropine, prazosin, yohimbine, propranolol, cimetidine, diphenhydramine, indomethacin or a mixture of methysergide and morphine. However, it was reduced by verapamil, a Ca2+ antagonist. Deletion of the N-terminal amino acid Tyr1 from the NPY molecule caused a 12-fold reduction of NPY potency as a coronary constrictor. Further shortening of the NPY molecule by removal of sequence Tyr1 through Glu15 or Tyr1 through Ala18 caused major losses of potency without detectable reduction of intrinsic activity. The results suggest that the constrictor effect of NPY on guinea pig coronary vessels results from a direct effect on vascular smooth muscle cells, is mediated by specific receptors and is likely to involve the participation of extracellular calcium ions. The results also suggest that the chemical groups responsible for the vasoconstrictor effect of NPY in guinea pig hearts might be scattered in the C-terminal end of the peptide.

Animals↗
PubMedDate not supplied

The cardiovascular response to epicardial application of neurotensin in guinea pigs.

Topical application of picomoles of neurotensin (NT) on the surface of the left ventricle (epicardial application) of anesthetized guinea pigs evoked dose-dependent pressor effects and tachycardia. The pressor response to epicardial NT was attenuated by pentolinium, a mixture of phentolamine and propranolol, or by guanethidine. However it was not affected by indomethacin, atropine or by a mixture of mepyramine and cimetidine. The tachycardia caused by epicardial NT was not modified by any of the aforementioned drugs. Both the pressor effects and tachycardia elicited by epicardial application of NT were markedly inhibited by chronic treatment of guinea pigs with capsaicin, and by topical application of lidocaine or tetrodotoxin to the surface of the left ventricle. Epicardial application of calcitonin gene-related peptide (CGRP), substance P (SP) or capsaicin also elicited tachycardia and either a decrease (CGRP and SP) or increase of blood pressure (capsaicin) in anesthetized guinea pigs. Epicardial application of NT, CGRP, or capsaicin in isolated, perfused hearts of guinea pigs also caused tachycardia. Together, these results suggest that the pressor responses to topical application of NT on the surface of the left ventricle in anesthetized guinea pigs are partially reflex in nature and likely to result from the stimulation by NT of cardiac sympathetic, capsaicin-sensitive, sensory nerve endings, whereas the tachycardia caused by epicardial NT appears to be due both to direct and indirect effects of NT on ventricular muscle cells. The possible participation of CGRP and/or SP in the chronotropic effect of NT applied on the epicardium, and their putative role as neurotransmitter of cardiac, capsaicin-sensitive, sensory neurons are discussed.

Angiotensin II↗
PubMedDate not supplied

Epicardial application of bradykinin elicits pressor effects and tachycardia in guinea pigs. Possible mechanisms.

Topical application of bradykinin (BK) to the surface of the left ventricle (epicardial application) of anesthetized guinea pigs elicited dose-dependent pressor effects and tachycardia. The pressor effect of epicardial BK was reduced by prior systemic treatment of animals with pentolinium or a combination of phentolamine and propranolol, but it was not affected by acute bilateral vagotomy or systemic administration of atropine, indomethacin, naloxone or a combination of mepyramine and cimetidine. The tachycardia caused by epicardial BK was not affected by any of the aforementioned drugs or by section of the vagi. Both the pressor effect and tachycardia evoked by epicardial BK were abolished by prior epicardial application of lidocaine, a local anesthetic, or by chronic systemic capsaicin treatment. These results suggest that the pressor effect of epicardial BK is partially reflex in nature and likely to result from the stimulation by BK of cardiac sympathetic, capsaicin-sensitive primary afferents, whereas the tachycardia caused by epicardial BK could be mediated by an intracardiac release of (a) cardioaccelerating substance(s) from cardiac, capsaicin-sensitive sensory nerve fibers and/or terminals.

Animals↗
PubMedDate not supplied

Participation of capsaicin-sensitive neurons in the cardiovascular effects of neurotensin in guinea pigs.

Intravenous (IV) infusions of neurotensin (NT) in anesthetized guinea pigs elicited dose-dependent pressor effects and tachycardia. Both effects were significantly reduced or abolished in guinea pigs given a chronic treatment with the neurotoxin capsaicin. In guinea pig isolated atria NT evoked a positive inotropic and chronotropic effect. Both effects were completely abolished in atria derived from capsaicin-treated guinea pigs. The positive inotropic and chronotropic effects of NT in guinea pig atria were mimicked by capsaicin and calcitonin gene-related peptide (CGRP). These results were interpreted as an indication that NT produces its cardiovascular effects in guinea pigs by activating capsaicin-sensitive sensory neurons.

Acetylcholine↗
PubMedDate not supplied

Capsaicin-sensitive structures as potential target sites for neurotensin and bradykinin in guinea pig atria.

We tested the influence of capsaicin (CAP) desensitization on the positive chronotropic and inotropic effects of neurotensin (NT), bradykinin (BK), calcitonin gene-related peptide (CGRP) and noradrenaline (NA) in guinea pig isolated atria. The positive chronotropic and inotropic effects of NT and BK were completely inhibited, whereas those elicited by CGRP and NA were either slightly reduced (CGRP) or unaffected (NA), in CAP-desensitized compared to control atria. Cross-desensitization studies using CAP, NT and BK showed that the positive chronotropic and inotropic effects of CAP are slightly affected, whereas those evoked by BK are markedly reduced in NT-desensitized atria. On the other hand, the positive chronotropic and inotropic effects of CAP and NT were similar in BK-desensitized and control atria. The results were interpreted as an indication that NT, BK and CAP produce their excitatory effects in guinea pig atria by interacting with a common population of CAP-sensitive sensory nerve fibers (presumably substance P (SP)- and CGRP-containing nerve fibers). The absence of cross-desensitization between NT or BK and CAP, or between NT and BK, suggests that the activation and desensitization of atrial, CAP-sensitive sensory nerve fibers by the latter agents involve different receptors and/or mechanisms.

Animals↗