Biomedical subjects

J M Arthur

Publications and source records attributed to J M Arthur.

26 records · Page 2Linked to original sources

PubMed1993

Partial agonist properties of rauwolscine and yohimbine for the inhibition of adenylyl cyclase by recombinant human 5-HT1A receptors.

Previous studies by another group have suggested that the alpha 2-adrenergic receptor antagonist rauwolscine may function as an agonist at the serotonin1A (5-HT1A) receptor expressed in human brain. To directly test that hypothesis, we transfected the human 5-HT1A receptor cDNA into CHO cells and examined the ability of rauwolscine and its isomer, yohimbine, to inhibit ligand binding of [3H]-(+/-)-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) and the activity of adenylyl cyclase in membranes derived from a single transformant that stably expresses approximately 225 fmol of 5-HT1A receptor/mg of membrane protein. Both ligands competitively antagonized the binding of [3H]8-OH-DPAT (Ki = 158 +/- 69 nM for rauwolscine and 690 +/- 223 nM for yohimbine), yielding shallow displacement curves consistent with agonist activity (Hill values = 0.69 +/- 0.2 for rauwolscine and 0.63 +/- 0.06 for yohimbine). Both ligands also inhibited forskolin-stimulated adenylyl cyclase activity in membranes derived from transfected (but not nontransfected) cells. For rauwolscine, the IC50 was 1.5 +/- 0.2 microM, and for yohimbine 4.6 +/- 1.0 microM, with activity ratios of 0.70 and 0.59, respectively, when compared to the full agonist serotonin. These studies demonstrated that rauwolscine and yohimbine are partial agonists for the human 5-HT1A receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1991

Role of medullary lateral reticular formation in baroreflex coronary vasoconstriction.

We have recently identified a polysynaptic pathway traversing discrete regions of the hypothalamus, midbrain, and medulla, along which site-specific electrical and chemical activation produces coronary vasoconstriction as part of a sympathoexcitatory response. We tested for the potential functional significance of this pathway by examining the hypothesis that a medullary component is involved in carotid baroreflex induced coronary vasoconstriction. Coronary flow velocity was measured with a Doppler probe in anesthetized cats. Following vagotomy and propranolol, bilateral carotid occlusion produced an increase in mean arterial pressure (56 +/- 14%, means +/- S.E.M.) and in coronary vascular resistance (51 +/- 13%) which was greater than that (29 +/- 6%) expected from the concurrent rise in arterial pressure during aortic constriction. Bilateral microinjections of lidocaine into the medullary lateral reticular formation attenuated the reflex increase in pressure (11 +/- 2%) and virtually abolished the rise (8 +/- 2%) in coronary resistance. After one hour recovery, carotid occlusion again increased aortic pressure (56 +/- 13%) and coronary vascular resistance (47 +/- 15%). Microinjections of lidocaine outside this medullary region did not impair the coronary vasoconstrictor response to carotid occlusion. We conclude that the medullary lateral reticular formation contains neural elements which participate in baroreflex-induced changes in arterial pressure and coronary vascular resistance. Components of the previously described central coronary vasoconstrictor pathway may play a role in pathophysiological conditions associated with increased coronary vasomotor tone.

Animals↗

PubMed1991

Coronary vasoconstriction during stimulation in hypothalamic defense region.

Previous studies have identified a site in lateral hypothalamus (LH) in which electrical stimulation elicits coronary vasoconstriction. We injected the retrogradely transported tracer Fast Blue to determine which brain regions project to LH. Projections to or through LH were found from the paraventricular nucleus (PVN) of the hypothalamus, bed nucleus of the stria terminalis (BNST), and dorsal raphe nucleus (DRN). In chloralose-anesthetized cats, electrical stimulation in DRN and BNST failed to increase coronary vascular resistance (CVR). However, stimulation lateral to PVN in the anterior hypothalamic area (AHA), a region not labeled by the tracer, caused a transient decrease in coronary blood flow similar to that elicited from LH. The increase in CVR was accompanied by hemodynamic changes that are characteristic of the defense reaction including a cholinergically mediated decrease in hindquarter vascular resistance. This response is likely due to activation of fibers of passage and not cell bodies, since cell bodies in the region were not retrogradely labeled and coronary vasoconstriction was not seen following microinjection of several excitatory amino acids into AHA. These data suggest that coronary vasoconstriction may be a component of the defense reaction elicited by electrical activation of AHA.

Amidines↗

PubMed1989

Characterization of coronary vasoconstrictor site in medullary reticular formation.

The importance of sympathetic neural influences in regulating coronary blood flow has been well established. However, central nervous system pathways responsible for these effects are largely unknown. In a feline model, we have identified a site in medullary reticular formation that may play a role in neural control of the coronary circulation. Changes in heart rate (HR), mean arterial pressure (AP), Doppler coronary flow velocity (CBFV), and femoral flow velocity (FBFV) were measured in 67 anesthetized cats. Electrical stimulation in a specific region of the right medullary lateral reticular formation produced elevations in HR (12 +/- 2% from 156 beats/min), AP (41 +/- 6% from 83 mmHg), CBFV (33 +/- 7%), and femoral vascular resistance index (136 +/- 27%). After beta-adrenergic blockade (propranolol), a transient (5-15 s) stimulus-induced decrease in CBFV was observed in 67% of animals, with a 55 +/- 6% increase in coronary vascular resistance index, not the result of autoregulation. Ipsilateral stellate ganglionectomy or systemic alpha 1-adrenergic blockade abolished the CBFV decrement. Microinjection of L-glutamate into this medullary region failed to elicit either pressor or coronary vasomotor responses. It is concluded that electrical stimulation in a specific site within medullary reticular formation produces neurogenic coronary vasoconstriction as part of a more generalized activation of central sympathetic fibers. This brain stem site may play an important role in reflex or behaviorally mediated coronary responses.

Adrenergic beta-Antagonists↗

PubMed1987

Electrical stimulation in perifornical lateral hypothalamus decreases coronary blood flow in cats.

Based on evidence implicating the central nervous system in the regulation of coronary vascular resistance and the knowledge that the hypothalamus is a central site for integration of cardiovascular control, studies were undertaken to determine if electrical stimulation in the hypothalamus produced coronary vasoconstriction. In anesthetized cats, following beta-adrenergic receptor blockade, stimulation in perifornical lateral hypothalamus produced a transient decrease in coronary blood flow velocity (30 +/- 5%), a small pressor effect (7 +/- 2 mmHg), and an initial decrease in hindquarter blood flow velocity (51 +/- 5%). The decrease in coronary flow velocity, which had an onset latency of 1-3 s and a duration of 5-15 s, was abolished by ipsilateral stellate ganglionectomy and by intravenous and intracoronary prazosin. The coronary vasoconstriction produced by hypothalamic stimulation was not different from that produced by cardioaccelerator nerve stimulation. These results suggest that electrical stimulation of a hypothalamic site produces an alpha-adrenergic receptor-mediated decrease in coronary blood flow that is unmasked by beta-adrenergic receptor blockade, requires the integrity of ipsilateral cardiac sympathetic innervation, and mimics the coronary response to cardioaccelerator nerve stimulation.

Adrenergic beta-Antagonists↗

PubMed1987

Neurogenic regulation of coronary blood flow: evidence for a central nervous system pathway.

The central representation of neurogenically mediated coronary vasoconstriction produced by activation of the sympathetic nervous system was examined in anesthetized cats instrumented for continuous recording of coronary and femoral blood flows, arterial pressure, and heart rate. Electrical stimulation in a small region of perifornical lateral hypothalamus increased arterial pressure, heart rate, and coronary blood flow; following the administration of propranolol, a transient coronary vasoconstrictor response was unmasked. The response was mediated over the sympathetic nervous system since it was blocked by stellate ganglionectomy and by the alpha 1-adrenergic receptor antagonist prazosin. Projections to and from the lateral hypothalamic site were identified by using anterograde and retrograde pathway-tracing techniques. Paraventricular nucleus projected to lateral hypothalamus, which in turn made connections in periaqueductal gray with projections terminating in lateral reticular formation of medulla. Coronary vasoconstrictor responses qualitatively identical to those produced by hypothalamic stimulation were found with activation of paraventricular nucleus and lateral reticular formation. Interruption of neuronal transmission in the medullary site blocked the response produced by activation of hypothalamic site. These data demonstrate that coronary vasoconstriction mediated over the sympathetic nervous system can be elicited from an interconnected pathway that links sympathoexcitatory sites in forebrain and brainstem.

Animals↗

PubMed1980

Morning plasma cortisol levels in infants treated with topical fluorinated glucocorticosteroids.

The plasma cortisol levels of 17 infants of mean age 12.1 months taken at 8 AM were measured before and after application of a topical fluorinated glucocorticosteroid. There was a statistically significant depression of plasma cortisol value in 11 infants at days 3, 7, and 14 after therapy. All of the plasma cortisol levels returned to normal. For the entire group of 17 infants, however, there was no significant depression of plasma cortisol levels. Even in the usual office use of topical glucocorticosteroids, one must be aware of the possiblity of percutaneous absorption.

Absorption↗

PubMedDate not supplied

Fentanyl and lidocaine versus lidocaine for Bier block.

BACKGROUND AND OBJECTIVES: The present study was designed to assess the efficacy of fentanyl combined with dilute lidocaine solution for intravenous regional anesthesia of the arm. METHODS: In ten volunteers, the nondominant arm was exposed to three treatments: 100 mg lidocaine, 42 ml; 100 mg lidocaine plus 100 micrograms fentanyl, 42 ml; and 100 micrograms fentanyl, 42 ml. Each subject was tested on three occasions with three or more days between experiments. Sensory and motor function was tested to determine whether the neural effects of the particular treatments differed. RESULTS: When lidocaine and lidocaine plus fentanyl results were compared, no significant differences were found. However, anesthesia, analgesia, and loss of motor function generally were less complete and slower in onset with the fentanyl alone treatment. Two subjects became nauseated after tourniquet cuff deflation when lidocaine plus fentanyl was tested, as did one subject when fentanyl was tested. CONCLUSION: Results of this and other studies indicate there is no value in adding fentanyl to local anesthetics for intravenous regional anesthesia.

Adult↗