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J De Champlain

Publications and source records attributed to J De Champlain.

At least 19 recordsLinked to original sources
PubMed1996

Receptor and mechanism that mediate endothelin- and big endothelin-1-induced phosphoinositide hydrolysis in the rat spinal cord.

In rat spinal cord slices, endothelin-1 and endothelin-3 enhanced [3H]inositol phosphate production between 1 nM and 10 microM (endothelin-1 > endothelin-3) while sarafotoxin 6c and the endothelin ETB receptor agonist IRL-1620 (Suc-[Glu9,Ala11,15]endothelin-1-(8-21)) were almost ineffective. BQ-123 (cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu), a selective endothelin ETA receptor antagonist, reduced the endothelin-1- and endothelin-3-induced [3H]inositol phosphate production, with similar inhibition constants (IC50: 16.7 +/- 3.4 and 8.0 +/- 1.6 microM, respectively). The inhibition of endothelin-1 was enhanced when BQ-123 was preincubated for 30 min instead of 15 min. BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1-methoxy- carbonyltryptophanyl-D-Nle), a selective ETB receptor antagonist, did not modify the endothelin-1-induced [3H]inositol phosphate production. Big endothelin-1 (1 nM to 1 microM) was slightly less potent than endothelin-1 in enhancing [3H]inositol phosphate production. This response was sensitive to phosphoramidon and [Phe22]big endothelin-1-(19-37), two inhibitors of endothelin-converting enzyme. Pretreatment of slices with pertussis toxin, indomethacin or PN 200-110 ((-)-isradipine, a dual inhibitor of L- and R-type Ca2+ channels) did not alter the response to 1 microM endothelin-1 while this response was abolished by tetrodotoxin. Finally, endothelin-1 enhanced [3H]inositol phosphate production with an identical EC50 (2.1 nM) in spinal cord slices of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) although the maximal response was reduced in SHR. These data indicate that endothelins stimulated [3H]inositol phosphate production in the rat spinal cord through the activation of an endothelin ETA receptor that trigger the release of an unidentified neurotransmitter. This effect does not appear to be associated to activation of a Gi/G(o)-type of G-protein, dihydropyridine-sensitive L-type Ca2+ channels or to the production of prostaglandins. Furthermore, the findings support the presence of a phosphoramidon-sensitive endothelin-converting enzyme in the spinal cord.

Animals↗
PubMed1994

Constitutive nonexocytotic norepinephrine release in sympathetic curves of in situ canine heart.

Nonexocytotic norepinephrine bulk overflow from sympathetic nerves has been previously demonstrated in the perfused isolated heart only after inhibition of sympathetic nerve metabolism by hypoxia, ischemia, or metabolic inhibitors. The measurement, however, ignores simultaneous uptake of norepinephrine by sympathetic nerves. We quantitated simultaneous norepinephrine uptake and release in pentobarbital-anesthetized dogs by the use of a transient tracer approach, the multiple indicator dilution technique, combined with measurement of endogenous arterial and venous plasma norepinephrine levels. Sympathetic vesicles were previously depleted by reserpine, and desipramine was used to inhibit the neuronal membrane pump. Labeled albumin, sucrose, and norepinephrine were injected into the coronary artery, and sequential samples were collected from the coronary sinus. Reserpine pretreatment significantly depleted tissue and decreased plasma norepinephrine levels; tracer norepinephrine uptake increased slightly, and there was a substantial decrease in the rate of release of unlabeled norepinephrine. Desipramine then decreased tracer uptake and virtually eliminated norepinephrine release. We conclude that desipramine-suppressible, constitutive nonexocytotic norepinephrine release is present in cardiac sympathetic nerves.

Animals↗
PubMed1993

Presynaptic effects of epinephrine on norepinephrine release from cardiac sympathetic nerves in dogs.

The possible functional role of tissue epinephrine in the modulation of norepinephrine release from cardiac sympathetic nerve endings in anesthetized dog was investigated. Observations were carried out under control conditions and after a short- (10 min) and long-term (180 min) epinephrine infusion (92 ng.kg-1.min-1). An increase in the stimulation-induced release of norepinephrine after intravenous administration of a selective beta 2-agonist (fenoterol, 0.5 micrograms/kg) indicated the presence of the beta 2-facilitatory mechanism. Furthermore, the facilitatory effect of fenoterol was inhibited by intravenous administration of a selective beta 2-antagonist (ICI 118551, 1 mg/kg). Short-term epinephrine infusion did not facilitate the stimulation-induced release of norepinephrine, when tissue epinephrine content in the left ventricle was increased 1.5-fold, without, as well as with, alpha 2-blockade (yohimbine, 0.3 mg/kg). However, stimulation-induced release of norepinephrine from the myocardium was significantly potentiated in animals in which tissue epinephrine in the left ventricle was greatly increased (5.6-fold) by a prolonged infusion of epinephrine (180 min). It is concluded that a facilitatory mechanism mediated by presynaptic beta 2-adrenoceptors is present in cardiac sympathetic nerve endings of the dog. Some of our observations support the hypothesis that this mechanism may be influenced by locally released epinephrine and, thus, by tissue epinephrine content.

Animals↗
PubMed1993

Effects of nifedipine and Bay K 8644 on stimulation-induced adrenal catecholamine secretion in the dog.

The effects of nifedipine and BAY K 8644 on the adrenal medullary secretion in response to direct splanchnic nerve stimulation were studied in anesthetized dogs. Supramaximal stimulation (12 V) was given on the left splanchnic nerve at a frequency of 2 Hz with three different pulse durations (0.2, 2, and 20 ms) for a total period of 1.5 min. Each stimulation was given for 30 s without interruption between each stimulation. Plasma concentrations of epinephrine and norepinephrine were measured in adrenal venous and aortic blood. In the vehicle control group, epinephrine and norepinephrine concentrations in adrenal venous blood proportionally increased with the lengthening of the pulse duration without significant changes in catecholamine concentrations in aortic blood. In dogs receiving nifedipine (100 micrograms/kg iv), the net increase in adrenal venous epinephrine concentration during stimulation with 20-ms pulse duration was attenuated by approximately 50% (P < 0.05). In dogs treated with BAY K 8644 (30 micrograms.kg-1.min-1 iv), both adrenal venous epinephrine and norepinephrine secretions evoked by stimulation with 20-ms pulse duration were significantly enhanced by approximately 50%. The present results suggest that the secretion of adrenal catecholamines under in vivo conditions is controlled through mechanism(s) involving dihydropyridine sensitive L-type Ca2+ channels presumably localized on the surface of adrenal medullary chromaffin cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Regulation of cardiovascular sympathetic neurons by substance P and gamma-aminobutyric acid in the rat spinal cord.

The spinal regulation of cardiovascular sympathetic preganglionic neurons by substance P (SP) and gamma-aminobutyric acid (GABA) was investigated in conscious rats. Intrathecal injection at the T-9 spinal level of bicuculline, a GABAA receptor antagonist, evoked increases in mean arterial pressure (MAP) and heart rate (HR) which were maximal at 5.0 and 0.5 nmol, respectively. Phaclofen, a GABAB receptor antagonist, produced no cardiovascular changes up to 2 mumol while 10 mumol evoked a rise in MAP and HR. Muscimol, a GABAA receptor agonist, produced a decrease in MAP which was maximal at 5.0 nmol and had no effect on HR. Baclofen, a GABAB receptor agonist, was without cardiovascular effects up to 5.0 nmol, while 50 and 100 nmol evoked a fall in MAP and HR. The pressor response to SP (16.25 nmol, T-9) was antagonised by 0.5-50 nmol muscimol or baclofen in a dose-related manner and the pressor response to SP was still inhibited by 40 nmol GABA in capsaicin-treated animals. However, when SP was injected at T-2, the rise in both MAP and HR was blocked by 50 nmol baclofen. Similarly, 50 nmol muscimol blocked the rise in both MAP and HR induced by 15 nmol thyrotropin-releasing hormone. In contrast, 50 nmol glycine failed to alter the cardiovascular response to SP co-injected either at T-9 or T-2. Baclofen was found to reduce significantly the basal release of epinephrine when injected at the T-9 level. These results provide pharmacological evidence for a possible tonic GABAergic inhibitory input onto cardiovascular sympathetic preganglionic neurons mediated by GABAA and GABAB receptors.

Animals↗
PubMed1989

Effect of sotalol against reperfusion-induced arrhythmias in Sprague-Dawley and Wistar rats.

The effect of (+/-)-sotalol (a beta-blocker with class III antiarrhythmic activity) against reperfusion-induced arrhythmias was studied in artificially ventilated, open-chest, Sprague-Dawley and Wistar rats. Coronary artery occlusion was produced for 5 min and reperfusion allowed for 10 min. A somewhat different arrhythmic profile was observed between saline-treated rats of the 2 strains studied, with more Sprague-Dawley rats experiencing an irreversible ventricular fibrillation (VF) upon reperfusion, compared to Wistar rats, in whom a combination of reversible ventricular tachycardia (VT) and VF was more frequently observed. No difference in action potential characteristics and ventricular effective refractory period determined in vitro, nor in myocardial noradrenaline content, was found between the 2 strains of rats. (+/-)-Sotalol (5 and 10 mg/kg, IV) showed marked beta-blocking activity and reduced the mean duration of VT-VF in both strains studied. It also produced similar increases in action potential duration and refractory period in vitro in these 2 strains. In a different series of experiments, the antiarrhythmic action of the racemic form was compared to that of (+)-sotalol using Wistar rats. (+)-Sotalol had much less beta-blocking activity, and was found to be similarly effective against reperfusion-induced VT-VF. It is concluded that the antiarrhythmic effect of sotalol against reperfusion-induced arrhythmias may not be related to beta-adrenergic blockade but probably to class III type activity. Despite differences in the profile of reperfusion-induced arrhythmias between Sprague-Dawley and Wistar rats, both strains were sensitive to the antiarrhythmic action of (+/-)-sotalol.

Animals↗
PubMed1988

Epinephrine release from the heart during left stellate ganglion stimulation in dogs.

Plasma epinephrine (E) and norepinephrine (NE) concentrations were measured (radioenzymatic assay) in blood samples simultaneously withdrawn from the aorta (Ao) and coronary sinus (CS) on 10 anesthetized dogs immediately before and during a 1-min period of electrical stimulation of the left stellate ganglion (4 V, 4 ms, 10 Hz). Heart rate and systolic blood pressure significantly increased in response to electrical stimulation (152 +/- 8 to 180 +/- 15 beats/min and 128 +/- 12 to 149 +/- 12 mmHg, mean +/- SE; P less than 0.05). Plasma NE concentrations were not significantly different in the Ao and the CS (432 +/- 110 and 319 +/- 67 pg/ml) before the stimulation, whereas a net removal of E was present across the myocardium (Ao, 172 +/- 61; CS, 71 +/- 22 pg/ml). A large NE spillover in the CS was observed during the stimulation (Ao, 1,555 +/- 513; CS, 10,583 +/- 3,753 pg/ml). A significant output of E from the myocardium was also present (Ao, 165 +/- 42; CS, 291 +/- 74 pg/ml) during the stimulation. Determination of NE and E concentrations by high-performance liquid chromatography in five of the dogs confirmed the observation made with the radioenzymatic assay, i.e., a significant uptake (66%) of blood-borne E was present across the myocardium in the control situation (Ao, 320 +/- 97; CS, 110 +/- 23 pg/ml), whereas plasma E concentrations in the CS (280 +/- 61 pg/ml) were 1.5 times the values found in Ao (184 +/- 56 pg/ml) under electrical stimulation. These observations give further support to the hypothesis that endogenous tissue E can act as a cotransmitter of sympathetic fibers.

Animals↗
PubMed1988

Increased inositol monophosphate production in cardiovascular tissues of DOCA-salt hypertensive rats.

The purpose of the present study was to investigate alpha 1-adrenergic receptors in the heart as well as the activity and the sensitivity of the phosphoinositide pathway on tissue slices of atria, ventricles, and femoral artery of hypertensive rats treated for 4 weeks with deoxycorticosterone acetate (DOCA) and 1% saline. DOCA-salt hypertensive rats were characterized by an increased sympathoadrenal tone, as suggested by increased norepinephrine and epinephrine plasma levels. The basal activity of the phosphoinositide pathway, estimated by measuring the accumulation of inositol monophosphate in the presence of an excess of lithium, was found to be greater in atria than in ventricles and femoral artery in both normotensive and DOCA-salt hypertensive rats, but it was twofold greater in atria and ventricles of DOCA-salt hypertensive rats compared with normotensive rats. Following stimulation by norepinephrine, the production of inositol monophosphate was greater in atria and femoral artery than in ventricles in both groups. However, in DOCA-salt hypertensive rats, the production of inositol monophosphate was markedly enhanced, being about twofold greater in atria and femoral artery and about three times greater in ventricles than in tissues of normotensive rats. These differences between DOCA-salt hypertensive and normotensive animals do not appear to be associated with a difference in alpha 1-adrenergic receptor number or affinity since cardiac alpha 1-adrenergic receptor number was unchanged in hypertensive rats and the binding affinity to the receptor was significantly decreased in hypertensive rats compared with normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Chronic renal and neurohumoral effects of the calcium entry blocker nisoldipine in patients with congestive heart failure.

Nisoldipine, a calcium entry blocker, was given to 10 patients with congestive heart failure. During a 2 month follow-up period, 7 of the 10 patients were readmitted with pulmonary edema; daily furosemide doses were increased (128 +/- 87 to 192 +/- 135 mg/day, p less than 0.01), and plasma creatinine increased (1.5 +/- 0.5 to 1.8 +/- 0.6 mg/dl, p less than 0.05) (all values mean +/- SD). Despite this unfavorable clinical course, nisoldipine caused some beneficial chronic (1 month) hemodynamic effects. It decreased systemic vascular resistance (from 1,781 +/- 229 to 1,306 +/- 345 dynes X s X cm-5, p less than 0.01), decreased mean arterial pressure (from 88 +/- 0 to 74 +/- 4 mm Hg, p less than 0.001) and increased stroke volume index (from 27 +/- 6 to 33 +/- 9 ml/min per m2, p less than 0.02). Heart rate, pulmonary capillary wedge pressure and stroke work index did not change. However, nisoldipine's chronic renal and neurohumoral effects were not as favorable. These were assessed during a 5 hour water load (15 ml/kg body weight of 5% dextrose in water) and compared with the effects of a water load before therapy. Nisoldipine did not change creatinine clearance or sodium excretion, but decreased water excretion (from 58 +/- 35 to 46 +/- 40% of water load in 5 hours). Over this 5 hour study, mean plasma vasopressin was also higher with nisoldipine (1.9 +/- 2.3 versus 2.7 +/- 3.2 pg/ml, p less than 0.05), but mean plasma aldosterone was lower (67 +/- 31 to 47 +/- 27 mg/dl, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Water↗
PubMed1986

Effects of sotalol, (-)-propranolol and prazosin on reperfusion-induced arrhythmias and increased cardiac norepinephrine release.

The pharmacological actions of sotalol, (-)-propranolol and prazosin on norepinephrine (NE) concentration and creatine kinase (CK) activity in the coronary sinus blood of the ischemic heart were studied in open-chest dogs. A 60 min occlusion of the left anterior descending coronary artery was followed by a reperfusion period of 30 min. In saline-treated dogs, a significant increase in coronary sinus NE concentration occurring 30 s after the onset of reperfusion was followed by a rapid decrease to the initial value within 15 min. CK activity increased gradually and continuously starting 5 min after the beginning of reperfusion. A good correlation (r = 0.9, n = 8, P less than 0.05) was obtained in saline-treated dogs when the calculated slope of the time-activity curves for CK release was plotted against the corresponding peak concentration of NE. The increase in coronary sinus NE concentration upon reperfusion was accompanied by an increased arrhythmic ratio. Sotalol (5 mg/kg i.v.) diminished the increase in coronary sinus NE concentration along with a significant decrease in the arrhythmic ratio. The administration of either (-)-propranolol (0.1 mg/kg i.v.) or prazosin (1 mg/kg i.v.) did not significantly affect the increase in coronary sinus NE concentration. The arrhythmic ratio was significantly reduced by prazosin but not by (-)-propranolol. The rise in coronary sinus CK activity was significantly diminished in the presence of either sotalol, (-)-propranolol or prazosin. These results suggest that the occurrence of severe ventricular arrhythmias upon reperfusion may be related to the action of the increased myocardial NE on the cardiac alpha-adrenoceptors. The increased coronary sinus CK activity suggests that increased cardiac sympathetic activation may accelerate or aggravate the myocardial damage. We conclude that the antiarrythmic effect of sotalol may be due at least in part to its inhibitory action on the release of cardiac NE upon reperfusion.

Adrenergic beta-Antagonists↗
PubMed1982

Skeletal muscle and cardiac changes with training in patients with angina pectoris.

Cardiovascular and skeletal muscle adaptations were studied before and after 6 mo of physical training in patients with coronary artery disease and exertional angina pectoris. Symptom-limited exercise capacity increased by 41% (470 +/- 30 to 665 +/- 35 kg.m.min-1; n = 29, P less than 0.001) with training as did skeletal muscle succinate dehydrogenase activity (1.75 +/- 0.24 to 3.31 +/- 0.24 IU; n = 23, P less than 0.001) and the areas of muscle fibers (type I from 43.6 +/- 3.3 to 54.4 +/- 3.3 micrometers 2 X 10(2); n = 21, P less than 0.05 and type II from 43.9 +/- 2.4 to 57.2 +/- 5.1 micrometers 2 X 10(2); P less than 0.01). At the same submaximal exercise intensity (mean 355 +/- 100 km.m.min-1), plasma catecholamines (1.31 +/- 0.14 to 1.07 +/- 0.09 ng.ml-1; n = 13, P less than 0.05), heart rate (115 +/- 3 to 97 +/- 3 beats/min; n = 29, P less than 0.001), and systolic blood pressure (171 +/- 4 to 143 +2- 4 mmHg; n = 29, P less than 0.001) were significantly reduced after training. Maximal coronary sinus blood flow (192 +/- 10 to 208 +/- 9 ml.min-1; n = 29, P less than 0.05) and left ventricular oxygen consumption (23.2 +/- 1.5 to 25.8 +/- 1.6 ml.min-1; n = 24, P less than 0.05) were increased by 8 and 11%, respectively, after training. The improvement in exercise capacity with training in patients with exercise is secondary to a reduction in myocardial oxygen requirements during subangina levels of exercise and partly to a small increase in maximal myocardial oxygen consumption. The skeletal muscle adaptations with training were not related to other indices of training such as the reduced exercise heart rate or increased symptom-limited exercise capacity.

Adult↗
PubMed1978

Circulating catecholamines and systolic time intervals in labile and sustained hypertension.

1. Average supine circulating total catecholamine concentrations were found to be higher than the normal range in about 50% of patients with labile hypertension and in about 30% of patients with sustained essential hypertension. 2. These higher resting concentrations were mainly due to an increase in adrenaline in labile hypertension and to an increase in noradrenaline in sustained hypertension. 3. Patients with elevated catecholamine concentrations were also characterized by a higher heart rate, by an increased myocardial contractility and by greater hypotensive response after treatment with beta-adrenoreceptor blocking agents. 4. These studies suggest the existence of sub-groups of hypertensive patients with increased sympathetic tone.

Catecholamines↗
PubMed1977

Increased circulating plasma catecholamines and plasma renin activity in dogs after chemical sympathectomy with 6-hydroxydopamine.

Circulating plasma catecholamines, plasma renin activity, and other variables were measured in unanesthetized dogs before and after chemical sympathectomy with 6-hydroxydopamine (6-OHDA, 50 mg/kg). Chemical sympathectomy resulted in an immediate fall in mean arterial blood pressure and a delayed reduction in heart rate. Significant increases in plasma glucose and lactate concentrations, circulating plasma catecholamines, and plasma renin activity were found 24 h after 6-OHDA treatment. Circulating catecholamine levels decreased rapidly as time elapsed after sympathectomy and were half the initial values after 2 weeks. Plasma renin activity remained elevated during the 1st week after 6-OHDA treatment and returned to control levels during the 2nd week. Significant correlations were found between circulating catecholamines and heart rate mean arterial pressure, and plasma glucose and lactate concentrations. A significant correlation was also found between plasma renin activity and the mean arterial blood pressure. These results confirm that the adrenal medulla increases its catecholamine secretion rate into the circulation to compensate for the loss of adrenergic innervation after 6-OHDA treatment. They also indicate that the renin-angiotensin system represents another important compensatory mechanism for circulatory homeostasis in sympathectomized animals.

Animals↗