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Journal of Applied Physiology... Dec 1997It is not clear whether the altered thermoregulatory reflex control of the cutaneous circulation seen among phases of the menstrual cycle also occurs with the synthetic... (Clinical Trial)
Clinical Trial
It is not clear whether the altered thermoregulatory reflex control of the cutaneous circulation seen among phases of the menstrual cycle also occurs with the synthetic estrogen and progesterone in oral contraceptive pills and whether any such modifications include altered control of the cutaneous active vasodilator system. To address these questions, we conducted controlled whole body heating experiments in seven women at the end of the third week of hormone pills (HH) and at the end of the week of placebo/no pills (LH). A water-perfused suit was used to control body temperature. Laser Doppler flowmetry was used to monitor cutaneous blood flow at a control site and at a site at which noradrenergic vasoconstrictor control had been eliminated by iontophoresis of bretylium (BT), isolating the active cutaneous vasodilator system. The oral temperature (Tor) thresholds for cutaneous vasodilation were higher in HH at both control [37.09 +/- 0.12 vs. 36.83 +/- 0.07 degrees C (LH), P < 0.01] and BT-treated [37. 19 +/- 0.05 vs. 36.88 +/- 0.12 degrees C (LH), P < 0.01] sites. The Tor threshold for sweating was similarly shifted (HH: 37.15 +/- 0.11 degrees C vs. LH: 36.94 +/- 0.11 degrees C, P < 0.01). A rightward shift in the relationship of heart rate to Tor was seen in HH. The sensitivities (slopes of the responses vs. Tor) did not differ statistically between phases. The similar threshold shifts at control and BT-treated sites suggest that the hormones shift the function of the active vasodilator system to higher internal temperatures. The similarity of the shifts among thermoregulatory effectors suggests a centrally mediated action of these hormones.
Topics: Adult; Body Temperature; Bretylium Tosylate; Contraceptives, Oral, Hormonal; Female; Heart Rate; Hot Temperature; Humans; Laser-Doppler Flowmetry; Regional Blood Flow; Skin; Stress, Physiological; Sweating; Sympatholytics; Vasodilation
PubMed: 9390975
DOI: 10.1152/jappl.1997.83.6.2012 -
British Journal of Cancer Nov 1995Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the amount of dissolved oxygen in the plasma. That this actually occurs has not been... (Comparative Study)
Comparative Study
Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the amount of dissolved oxygen in the plasma. That this actually occurs has not been verified experimentally. This study was performed to explore changes in tumour oxygenation induced by treatment with normobaric and hyperbaric oxygen and carbogen. R3230Ac mammary adenocarcinomas were implanted into Fisher 344 rats. Arterial blood gases, blood pressure and heart rate were monitored. Tumour oxygenation was measured polarographically in five sets of animals. They received either normobaric 100% oxygen, hyperbaric (3 atmospheres; atm) 100% oxygen, normobaric carbogen or hyperbaric (3 atm) carbogen (HBC) +/- bretylium. HBO reduced the mean level of low pO2 values (< 5 mmHg) from 0.49 to 0.07 (P = 0.0003) and increased the average median pO2 from 8 mmHg to 55 mmHg (P = 0.001). HBC reduced the level of low pO2 values from 0.82 to 0.51 (P = 0.002) an increased median pO2 from 2 mmHg to 6 mmHg (P = 0.05). Normobaric oxygen and carbogen did not change tumour oxygenation significantly. Sympathetic blockade with bretylium before HBC exposure improved oxygenation significantly more than HBC alone (low pO2 0.55-0.17, median pO2 4-17 mmHg). HBO and hyperbaric carbogen improved tumour oxygenation in this model, while normobaric oxygen or carbogen had no effect. Sympathetic-mediated vasoconstriction during hyperbaric carbogen caused it to be less effective than HBO. This mechanism also appeared to operate during normobaric carbogen breathing.
Topics: Adenocarcinoma; Animals; Autonomic Nerve Block; Bretylium Tosylate; Carbon Dioxide; Cell Hypoxia; Female; Hyperbaric Oxygenation; Injections, Subcutaneous; Mammary Neoplasms, Experimental; Neoplasm Transplantation; Oxygen; Oxygen Consumption; Rats; Rats, Inbred F344; Sympatholytics; Vasoconstriction; Vasomotor System
PubMed: 7577456
DOI: 10.1038/bjc.1995.474 -
Quarterly Journal of Experimental... Oct 1981The diuretic response to stimulation of left atrial receptors by distending small balloons located at the pulmonary vein--left atrial junctions and in the left atrial...
The diuretic response to stimulation of left atrial receptors by distending small balloons located at the pulmonary vein--left atrial junctions and in the left atrial appendage was studied in anaesthetized dogs in which bretylium tosylate, atenolol and atropine had been administered to effect blockade of renal nerves and to prevent increases in heart rate resulting from stimulation of atrial receptors. In these dogs, distension of the balloons was not associated with significant changes in heart rate, left atrial pressure or arterial blood pressure, and resulted in increases in urine flow, decreases in urinary sodium concentration and no significant changes in urinary sodium excretion. It is concluded that the humoral mechanism is responsible for the diuresis in response to stimulation of atrial receptors and has no significant effect on the response of natriuresis known to involve a decrease in the activity in the renal nerves and haemodynamic changes associated with stimulation of atrial receptors.
Topics: Animals; Atenolol; Atropine; Blood Pressure; Bretylium Tosylate; Carbon Dioxide; Diuresis; Dogs; Heart Atria; Heart Rate; Hydrogen-Ion Concentration; Sensory Receptor Cells
PubMed: 6796989
DOI: 10.1113/expphysiol.1981.sp002585 -
The Journal of Clinical Investigation Jan 1990Proximal duodenal bicarbonate secretion is an important factor in humans and animals protecting the mucosa against acid-peptic damage. This study examined the mechanisms...
Proximal duodenal bicarbonate secretion is an important factor in humans and animals protecting the mucosa against acid-peptic damage. This study examined the mechanisms responsible for the central nervous system regulation of duodenal bicarbonate secretion by calcitonin gene-related peptide (CGRP) in unrestrained rats. Cerebroventricular administration of rat CGRP significantly inhibited basal duodenal bicarbonate secretion as well as the stimulatory effects of vasoactive intestinal peptide, neurotensin, a luminal PGE1 analogue, misoprostol, and hydrochloric acid. The inhibitory effects of cerebroventricular CGRP were abolished by ganglionic blockade with chlorisondamine, significantly attenuated by noradrenergic blockade with bretylium, and enhanced by vagotomy. Inhibition of duodenal bicarbonate secretion induced by CGRP coincided with significant increases in plasma norepinephrine (NE) and vasopressin concentrations. The alpha adrenergic receptor antagonist, phentolamine, and the vasopressin V1 receptor antagonist, (1-deaminopenicillamine, 2-[O-methyl]Tyr, 8-Arg)-vasopressin, given intravenously reversed the central inhibitory effect of CGRP by approximately 50% each. Pretreatment of the animals with both phentolamine and the vasopressin antagonist completely abolished the central inhibitory effect of CGRP. Peripheral vasopressin and NE significantly decreased duodenal bicarbonate secretion, and their inhibitory effects were additive and prevented by phentolamine and the vasopressin antagonist, respectively. We conclude that cerebroventricular CGRP inhibits rat duodenal bicarbonate secretion by activation of sympathetic efferents and subsequent release of NE and vasopressin that act on alpha adrenergic and vasopressin receptors, respectively.
Topics: Adrenalectomy; Animals; Arginine Vasopressin; Bicarbonates; Bretylium Compounds; Bretylium Tosylate; Calcitonin; Calcitonin Gene-Related Peptide; Cerebral Ventricles; Duodenum; Hypophysectomy; In Vitro Techniques; Injections, Intraventricular; Intestinal Mucosa; Male; Naloxone; Norepinephrine; Phentolamine; Rats; Rats, Inbred Strains; Reference Values; Vagotomy; Vasopressins
PubMed: 2295700
DOI: 10.1172/JCI114420 -
American Journal of Physiology. Heart... Apr 2005Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a... (Clinical Trial)
Clinical Trial
Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29 degrees C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (-14 +/- 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 +/- 7.7%) but did not affect the response at 30 min (-30.6 +/- 9% control, -38.9 +/- 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (-14.3 +/- 4.2% control) to vasodilation (+26.3 +/- 12.1% YP), without a significant effect on the 30-min response (-26.7 +/- 6.1% YP, -43.2 +/- 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction (P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (-20.1 +/- 6.4% control) to one of vasodilation (+213.4 +/- 87.0% Emla), whereas the final levels did not differ significantly (-37.7 +/- 10.1% control, -37.2 +/- 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.
Topics: Adrenergic Antagonists; Adrenergic alpha-Antagonists; Adult; Anesthetics, Local; Bretylium Tosylate; Cold Temperature; Female; Humans; Male; Neurons, Afferent; Receptors, Neuropeptide Y; Skin; Skin Temperature; Sympathetic Nervous System; Vasoconstriction; Yohimbine
PubMed: 15576441
DOI: 10.1152/ajpheart.00849.2004 -
American Journal of Physiology. Heart... Jul 2007Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves....
Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves. Six subjects participated. Local skin and body temperatures were controlled with Peltier probe holders and water-perfused suits, respectively. Skin blood flow at four forearm sites was monitored by laser-Doppler flowmetry with the following treatments: untreated control, pretreatment with local anesthesia (LA) blocking sensory nerve function, pretreatment with bretylium tosylate (BT) blocking VC nerve function, and pretreatment with both LA and BT. Local skin temperature was slowly reduced from 34 to 29 degrees C at all four sites. Both sites treated with LA produced an increase in cutaneous vascular conductance (CVC) early in the LC process (64 +/- 55%, LA only; 42 +/- 14% LA plus BT; P < 0.05), which was absent at the control and BT-only sites (5 +/- 8 and 6 +/- 8%, respectively; P > 0.05). As cooling continued, there were significant reductions in CVC at all sites (P < 0.05). At control and LA-only sites, CVC decreased by 39 +/- 4 and 46 +/- 8% of the original baseline values, which were significantly (P < 0.05) more than the reductions in CVC at the sites treated with BT and BT plus LA (-26 +/- 8 and -22 +/- 6%). Because LA affected only the short-term response to LC, either alone or in the presence of BT, we conclude that sensory nerves are involved early in the VC response to LC, but not for either adrenergic or nonadrenergic VC with longer term LC.
Topics: Afferent Pathways; Blood Flow Velocity; Body Temperature Regulation; Cold Temperature; Female; Humans; Male; Sensation; Skin; Skin Temperature; Vasoconstriction
PubMed: 17468334
DOI: 10.1152/ajpheart.00323.2007 -
British Journal of Pharmacology Oct 19691. The initial effect of bretylium tosylate on isolated rabbit atria was to increase conduction velocity, contraction heights, spontaneous frequency and maximum driven...
1. The initial effect of bretylium tosylate on isolated rabbit atria was to increase conduction velocity, contraction heights, spontaneous frequency and maximum driven frequency, and to reduce electrical threshold. At concentrations of 200 mg/l. or less, these were the only effects, and were consistent with the known sympathomimetic actions of bretylium.2. At extremely high concentrations, 1,200 and 2,400 mg/l., the initial actions were succeeded by weak quinidine-like effects; reduced conduction velocity, spontaneous and maximum driven frequencies, and rate of rise of action potential. The electrical threshold was raised, but contraction heights were not reduced.3. The local anaesthetic activity of bretylium, measured by reductions in the frog nerve action potential, was 1/90 that of procaine and 1/300 that of propranolol, on a molar basis.4. Acute pretreatment with bretylium, 20 mg/kg intravenously, significantly increased the amount of infused ouabain required before the appearance of the first signs of atrial arrhythmia in anaesthetized guinea-pigs, but did not prevent ventricular arrhythmias.5. Pretreatment with bretylium 30 mg/kg subcutaneously 24 hr, and again 4 hr before ouabain infusion, increased the dose of ouabain inducing atrial irregularity and slightly but significantly reduced the incidence of ventricular fibrillation.
Topics: Action Potentials; Anesthetics, Local; Animals; Anura; Arrhythmias, Cardiac; Bretylium Compounds; Guinea Pigs; Heart; Heart Atria; In Vitro Techniques; Ouabain; Procaine; Propranolol; Quinidine; Rabbits; Ventricular Fibrillation
PubMed: 5348427
DOI: No ID Found -
Bulletin of the New York Academy of... Sep 1979
Topics: Animals; Bretylium Compounds; Bretylium Tosylate; Catecholamines; Coronary Disease; Dobutamine; Humans
PubMed: 290401
DOI: No ID Found -
The Journal of Physiology Feb 19921. This study was undertaken to determine whether distension of the descending colon in anaesthetized dogs reflexly affects the heart rate, arterial blood pressure or...
1. This study was undertaken to determine whether distension of the descending colon in anaesthetized dogs reflexly affects the heart rate, arterial blood pressure or the left ventricular inotropic state. 2. Experiments were performed on twenty-six dogs, which were anaesthetized with sodium pentobarbitone and artificially ventilated. A segment of the distal descending colon was isolated and was distended with warm Ringer solution at a steady intraluminal pressure. 3. In each animal, distension of the colon caused an increase in heart rate and aortic blood pressure. The response of an increase in heart rate was augmented by preventing changes in aortic blood pressure, and was graded in seven dogs by step increments in the distending pressure. In the same animals, distension of the colon always caused a small increase in left ventricular (dP/dt)max at constant heart rate and aortic blood pressure. 4. In four of the twenty-six dogs, cutting the pelvic nerves did not abolish the observed responses to the distension. In seven of the twenty-six dogs, which included the four animals with sectioned pelvic nerves, cutting the hypogastric nerves completely abolished all the observed responses. 5. In thirteen of the twenty-six dogs, propranolol or bretylium tosylate completely abolished the reflex increases in heart rate and left ventricular (dP/dt)max, and phentolamine or bretylium tosylate abolished the reflex increase in aortic blood pressure. 6. These results showed that distension of the colon reflexly increased the heart rate, arterial blood pressure and left ventricular inotropic state. These reflex responses were mediated by sympathetic effects and their afferent limb involved the hypogastric nerves.
Topics: Animals; Blood Pressure; Colon; Dogs; Heart Rate; Hypogastric Plexus; Myocardial Contraction; Pelvis; Pressure; Ventricular Function
PubMed: 1593452
DOI: 10.1113/jphysiol.1992.sp019009 -
British Journal of Anaesthesia Mar 1978The effects of bilateral adrenalectomy, together with the i.v. administration of bretylium tosylate 20 mg kg-1 on halothane-induced malignant hyperthermia (MH), were...
The effects of bilateral adrenalectomy, together with the i.v. administration of bretylium tosylate 20 mg kg-1 on halothane-induced malignant hyperthermia (MH), were investigated in six Pietrain pigs. All six animals survived the halothane challenge, and failed to show any signs of increased muscle metabolism. Bilateral adrenalectomy alone prevented halothane-induced MH in three out of four Pietrain pigs, whereas the i.v. administration of bretylium alone protected only one pig out of an additional four animals studied. The results show that complete adrenergic blockade inhibits the susceptibility of Pietrain skeletal muscle to halothane and that the adrenal medulla makes an important contribution to this response.
Topics: Adrenalectomy; Anesthesia, General; Animals; Bretylium Compounds; Bretylium Tosylate; Halothane; Malignant Hyperthermia; Swine; Swine Diseases
PubMed: 637997
DOI: 10.1093/bja/50.3.241