Searched for: person:colemd08
in-biosketch:true
Part 1: Case 4. Wedge is 18; he must be full
Chapter by: Gallagher, Christopher; Coleman, Dominick A
in: Core clinical competencies in anesthesiology : a case-based approach by Gallagher, Christopher J; et al [Eds]
Cambridge ; New York : Cambridge University Press, 2010
pp. 28-33
ISBN: 9780521144131
CID: 5372502
Physiologic increases in extracellular sodium salt enhance coronary vasoconstriction and Ca2+ entry
Coleman, Dominick A; Khalil, Raouf A
High dietary sodium salt has been suggested to increase the risk of coronary vasospasm and coronary artery disease. However, whether high-sodium salt directly affects the mechanisms of coronary artery contraction is unclear. This study investigated whether physiologic and supraphysiologic increases in extracellular concentrations of sodium chloride ([NaCl]e) enhance the Ca2+ handling mechanisms of coronary smooth muscle contraction. Isometric contraction and 45Ca2+ influx were measured in endothelium-denuded porcine coronary artery strips incubated in Krebs solution (2.5 mM Ca2+) containing increasing [NaCl]e (120, 121, 123, 126, 130, 140, and 150 mM). Increasing [NaCl]e for 30 min did not increase the resting coronary tone or 45Ca2+ influx. 5-Hydroxytryptamine (5-HT) caused concentration-dependent increases in contraction and 45Ca2+ influx. Preincubation of coronary strips in increasing [NaCl]e for 30 min did not change the median effective dose of 5-HT. However, the magnitude of the 5-HT contraction and 45Ca2+ influx was significantly increased at 121-126 mM [NaCl]e. Preincubation with 2,4-dichlorobenzamil (10-5 M), inhibitor of the Na+/Ca2+ exchanger, or KB-R7943 (10-5 M), selective inhibitor of the reverse mode of the Na+/Ca2+ exchanger, abolished the increases in 5-HT contraction and 45Ca2+ influx at 121-126 mM [NaCl]e. Preincubation in Krebs solution containing 120 mM NaCl plus 1-6 mM LiCl or N-methyl-d-glucamine did not increase 5-HT contraction or 45Ca2+ influx. Higher [NaCl]e (140-150 mM) increased 5-HT-induced 45Ca2+ influx but inhibited 5-HT contraction. 5-HT (10-5 M)- and caffeine (25 mM)-induced contraction in Ca2+-free (2 mM EGTA) solution, a measure of Ca2+ release from the intracellular stores, was not affected by small increases in [NaCl]e (121-126 mM) but was inhibited at higher [NaCl]e (130-150 mM). Thus increases in [NaCl]e within the physiologic range enhance coronary smooth muscle contraction to 5-HT by a mechanism possibly involving Ca2+ entry via the reverse mode of the Na+/Ca2+ exchanger, but not Ca2+ release from the intracellular stores. The reduction of coronary contraction with supraphysiologic [NaCl]e in both Ca2+-containing and Ca2+-free Krebs could be related to excessive increases in ionic strength and may mask significant coronary vasoconstrictor effects of physiologic increases in [NaCl]e.
PMID: 12072578
ISSN: 0160-2446
CID: 5372162
The nucleus paragigantocellularis and opioid withdrawal-like behavior
Rockhold, R W; Liu, N; Coleman, D; Commiskey, S; Shook, J; Ho, I K
Participation of the nucleus paragigantocellularis (PGi) in mediation of opioid withdrawal was examined in conscious, unrestrained, non-opioid-dependent rats, using electrical stimulation of the PGi. A characteristic series of behaviors, which resembled those seen during naloxone-precipitated withdrawal from dependence on the opioid agonist, butorphanol, was elicited during 30 min of PGi stimulation. Thus, the behavioral syndrome has been termed opioid withdrawal-like. Simultaneous microdialysis measurement of glutamate within the locus ceruleus indicated a positive correlation between extracellular glutamate concentrations and behavioral responses. Behavioral responses were inhibited by 50% during reverse dialysis perfusion of the locus ceruleus with the glutamate receptor antagonist, kynurenic acid, without any effect on glutamate concentrations. Thus, increases in locus ceruleus glutamate partially mediate opioid withdrawal-like behavior. Intracerebroventricular (i.c.v.) injections of the opioid antagonist, naloxone, or of the mu-selective (beta-funaltrexamine) or the delta-selective (naltrindole) opioid antagonists decreased, but did not abolish, stimulation-induced behavioral responses. Similar i.c.v. injections of the kappa-selective antagonist, nor-binaltorphimine, had no effect on behavioral responses to PGi stimulation. Activation of the PGi by electrical stimulation can elicit behaviors similar to those observed during opioid withdrawal. Moreover, additional levels of complexity are evident in the neuropharmacology of PGi stimulation-induced opioid withdrawal-like behavior.
PMID: 10810247
ISSN: 1021-7770
CID: 5372172