Linked Life Data

18071056

Source:http://linkedlifedata.com/resource/pubmed/id/18071056

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-24
pubmed:abstractText
The alpha(2)-adrenoceptor agonist clonidine reduces blood pressure more effectively in White than Black Americans despite similar degrees of sympatholysis. Functional genetic variation in receptor signaling mechanisms, for example in the beta 3 G-protein subunit (GNB3 C825T) and in the alpha(2C)-adrenoceptor subtype (ADRA2C del322-325), may affect drug responses. We examined the hypothesis that there are ethnic differences in the responses to the highly selective alpha(2)-agonist, dexmedetomidine, and that these genetic variants contribute to interindividual variability in drug responses. In a placebo-controlled, single-masked study, 73 healthy subjects (37 whites and 36 blacks) received 3 placebo infusions and then 3 incremental doses of dexmedetomidine (cumulative dose, 0.4 microg/kg), each separated by 30 minutes. Blood pressure, heart rate, and plasma catecholamine concentrations were determined after each infusion. We measured dexmedetomidine concentrations after the last infusion and determined ADRA2C del322-325 and GNB3 C825T genotypes. Dexmedetomidine lowered blood pressure and plasma catecholamine concentrations significantly (all P<0.001). There was substantial interindividual variability in the reduction of systolic blood pressure (range, 1 to 34 mm Hg) and plasma norepinephrine concentrations (range, 24 to 424 pg/mL). However, there were no differences between black and white subjects in dexmedetomidine responses (P>0.16 for all outcomes) before or after adjustment for covariates. Neither ADRA2C del322-325 nor GNB3 C825T genotypes affected the responses to dexmedetomidine (all P>0.66). There is large interindividual variability in response to the selective alpha(2)-AR agonist dexmedetomidine, and neither ethnicity nor ADRA2C and GNB3 genotypes contribute to it. Further studies to identify determinants of alpha(2)-AR-mediated responses will be of interest.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
406-11
pubmed:dateRevised
2010-12-17
pubmed:meshHeading
pubmed-meshheading:18071056-Adrenergic alpha-2 Receptor Agonists, pubmed-meshheading:18071056-Adrenergic alpha-Agonists, pubmed-meshheading:18071056-Adult, pubmed-meshheading:18071056-African Continental Ancestry Group, pubmed-meshheading:18071056-Blood Pressure, pubmed-meshheading:18071056-Cardiovascular System, pubmed-meshheading:18071056-Cytosine, pubmed-meshheading:18071056-Dexmedetomidine, pubmed-meshheading:18071056-European Continental Ancestry Group, pubmed-meshheading:18071056-Female, pubmed-meshheading:18071056-Genetic Variation, pubmed-meshheading:18071056-Genotype, pubmed-meshheading:18071056-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:18071056-Humans, pubmed-meshheading:18071056-Male, pubmed-meshheading:18071056-Norepinephrine, pubmed-meshheading:18071056-Osmolar Concentration, pubmed-meshheading:18071056-Receptors, Adrenergic, alpha-2, pubmed-meshheading:18071056-Sequence Deletion, pubmed-meshheading:18071056-Single-Blind Method, pubmed-meshheading:18071056-Thymine
pubmed:year
2008
pubmed:articleTitle
Ethnic and genetic determinants of cardiovascular response to the selective alpha 2-adrenoceptor agonist dexmedetomidine.
pubmed:affiliation
Department of Medicine, Division of Clinical Pharmacology, 542 RRB, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural