Dorsal hand vein responses to the α1-adrenoceptor agonist phenylephrine do not predict responses to the α2-adrenoceptor agonist dexmedetomidine

Posti, Jussi P.; Valve, Laura; Ruohonen, Saku; Akkila, Juha; Scheinin, Mika; Snapir, Amir

doi:10.1016/j.ejphar.2010.11.024

Cited by 7 publications

(15 citation statements)

References 24 publications

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“…4,5 We interpret these findings as suggesting that ethnic differences in α 1 -AR-mediated venoconstriction are more likely to be related to differences in pathways linked specifically to α 1 -AR signaling rather than to downstream vasoconstrictor mechanisms shared by α 1 -AR and α 2 -AR activation. Further studies will be necessary to elucidate factors contributing to ethnic differences in α 1 -AR-mediated vasoconstriction.…”

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confidence: 80%

Response to Is Creatine Kinase the Intrinsic Factor of Smooth Muscle Enhancing Vascular Contractility in Subjects of African Ancestry?

et al. 2013

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confidence: 80%

Response to Is Creatine Kinase the Intrinsic Factor of Smooth Muscle Enhancing Vascular Contractility in Subjects of African Ancestry?

et al. 2013

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“…For the GWAS, non-smoking Caucasian men and women aged 18 to 40 years were eligible if they were unrelated and healthy as assessed by medical history, physical examination, 12-lead electrocardiogram, blood count and serum lipid profile. Information on this study population has been published in an earlier report that analyzed subject characteristics contributing to the inter-individual variation in DHV responses to dexmedetomidine [6]. From the 99 subjects of the earlier report, all of whom had provided DNA samples for eventual later analysis, we selected 64 subjects who represented the low and high ends of the response range, based on their DHV constriction responses to dexmedetomidine (ED 50 values greater than 30 ng/min or less than 5 ng/min).…”

Section: Methodsmentioning

confidence: 99%

“…DHV responses were measured in supine subjects with a previously validated LVDT method, as described earlier [6,7]. In Turku, α 2 -AR-mediated DHV constriction was elicited by graded infusions of dexmedetomidine (Precedex®, Hospira, Lake Forest, IL, USA) into the investigated vein, with 8 consecutive dose rates ranging from 0.0128 to 1000 ng/min.…”

Section: Methodsmentioning

confidence: 99%

“…Log-transformed dexmedetomidine ED 50 was set as the dependent variable with sex, age and temperature of the infusion hand finger tip (mean temperature from the last 25 min of the drug infusion (see [6]) (discovery phase) or sex and age (replication phase) used as covariates. The linear regression model requires the dependent variable to be normally distributed.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we reported that factors such as gender, blood pressure, heart rate, blood lipids, plasma norepinephrine concentrations, hormonal contraception, menstrual cycle phase and blood haemoglobin concentration were not statistically significant determinants of DHV sensitivity to constriction after α 2 -AR activation by dexmedetomidine, the most selective clinically available α 2 -AR agonist [6]. Pharmacogenetic association studies of several candidate genes (i.e.…”

Section: Introductionmentioning

confidence: 99%

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A polymorphism in the protein kinase C gene PRKCB is associated with α2-adrenoceptor-mediated vasoconstriction

Posti

Salo²,

Ruohonen

et al. 2013

Pharmacogenetics and Genomics

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Objectives α2-Adrenoceptors (α2-AR) mediate both constriction and dilatation of blood vessels. There is substantial inter-individual variability in dorsal hand vein (DHV) constriction responses to α2-AR agonist activation. Genetic factors appear to contribute significantly to this variation. The present study was designed to identify genetic factors contributing to the inter-individual variability in α2-AR-mediated vascular constriction induced by the selective α2-AR agonist dexmedetomidine. Methods DHV constriction responses to local infusion of dexmedetomidine were assessed by measuring changes in vein diameter with a linear variable differential transformer. The outcome variable was log-transformed dexmedetomidine ED50 for constriction. A genome-wide association study (GWAS) of 433,378 single nucleotide polymorphisms (SNPs) was performed for the sensitivity of DHV responses in 64 healthy Finnish subjects. 20 SNPs were selected based on the GWAS results and their associations with the ED50 of dexmedetomidine were tested in an independent North American study population of 68 healthy individuals. Results In both study populations (GWAS and replication samples), the SNP rs9922316 in the gene for protein kinase C type β was consistently associated with dexmedetomidine ED50 for dorsal hand vein constriction (unadjusted p = 0.00016 for the combined population). Conclusions Genetic variation in protein kinase C type β may contribute to the inter-individual variation in dorsal hand vein constriction responses to α2-AR activation by the agonist dexmedetomidine.

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Genetic variation in the α1A-adrenergic receptor and phenylephrine-mediated venoconstriction

et al. 2014

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There is large interindividual variability and ethnic differences in phenylephrine-mediated vasoconstriction. We tested the hypothesis that genetic variation in ADRA1A, the α1A adrenergic receptor gene, contributes to the variability and ethnic differences. We measured local dorsal hand vein responses to increasing doses of phenylephrine in 64 Caucasians and 42 African-Americans and genotyped for 32 ADRA1A SNPs. The ED50 ranged from 11 to 5442 ng/min, and the Emax ranged from 13.5% to 100%. The rs574647 variant was associated with a trend towards lower logED50 in each race and in the combined cohort (P=0.008). Additionally, rs1079078 was associated with a trend to higher logED50 in each race and in the combined cohort (P=0.011). Neither variant accounted for the ethnic differences in response. None of the ADRA1A haplotypes was associated with the outcomes. In conclusion, ADRA1A variants do not contribute substantially to the marked interindividual variability or ethnic differences in phenylephrine-mediated venoconstriction.

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Dorsal hand vein responses to the α1-adrenoceptor agonist phenylephrine do not predict responses to the α2-adrenoceptor agonist dexmedetomidine

Cited by 7 publications

References 24 publications

Response to Is Creatine Kinase the Intrinsic Factor of Smooth Muscle Enhancing Vascular Contractility in Subjects of African Ancestry?

Response to Is Creatine Kinase the Intrinsic Factor of Smooth Muscle Enhancing Vascular Contractility in Subjects of African Ancestry?

A polymorphism in the protein kinase C gene PRKCB is associated with α2-adrenoceptor-mediated vasoconstriction

Genetic variation in the α1A-adrenergic receptor and phenylephrine-mediated venoconstriction

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