Effect of the α2C-adrenoreceptor deletion322–325 variant on sympathetic activity and cardiovascular measures in healthy subjects

Abstract

The ADRA2C deletion polymorphism had no effect on markers of resting sympathetic activity and cardiovascular measures, and did not account for ethnic differences in blood pressure.

Ethnic and Genetic Determinants of Cardiovascular Response to the Selective α 2 -Adrenoceptor Agonist Dexmedetomidine

“…5 However, larger studies found no associations between the ADRA2C deletion and markers of elevated resting sympathetic tone, blood pressure, or heart rate. 10,22 Variable results regarding the association between the ADRA2C deletion variant and cardiac function 14,23 suggest that the functional effects of the deletion variant may be most apparent in circumstances of substantially elevated sympathetic tone (eg, after yohimbine administration or in advanced congestive heart failure), and only in subjects who are homozygous for the deletion. 10,24 Another approach to examine the functional consequences of the ADRA2C deletion is to administer an ␣ 2 -AR agonist.…”

“…10,22 Variable results regarding the association between the ADRA2C deletion variant and cardiac function 14,23 suggest that the functional effects of the deletion variant may be most apparent in circumstances of substantially elevated sympathetic tone (eg, after yohimbine administration or in advanced congestive heart failure), and only in subjects who are homozygous for the deletion. 10,24 Another approach to examine the functional consequences of the ADRA2C deletion is to administer an ␣ 2 -AR agonist. A small study in healthy white Europeans found no effects of the deletion variant on blood pressure, heart rate, and plasma norepinephrine responses to clonidine, but among the 9 subjects carrying the deletion allele, only 3 were homozygous.…”

“…The ADRA2C del322-325 variant was genotyped by DNA fragment analysis as described previously, 10 and the GNB3 C825T polymorphism (rs5443) was performed by allelic discrimination with TaqMan 5Ј-nuclease assays. 11 Further details are available in the online supplement (please see http://hyper.ahajournals.org).…”

Pharmacogenomics of G Protein-Coupled Receptor Ligands in Cardiovascular Medicine

“…In theory, the reduced activity of the ␣ 2C -AR, with the deletion of amino acids 322 to 325, should lead to a reduced inhibition of NE release from the presynaptic nerve terminals and ultimately result in increased adrenergic drive. However, in healthy persons, basal parameters of the sympathetic nervous system, including heart rate, heart rate variability, blood pressure, and concentrations of NE and EPI were not affected by this variant (Table 4) (Kurnik et al, 2007). Intravenous administration of the ␣ 2 -agonist dexmedetomidine to healthy subjects results in blood pressure lowering and a decrease in plasma catecholamine concentrations.…”

Associação de betabloqueadores e treinamento físico na insuficiência cardíaca de camundongos

“…These mice develop clinical signs of HF such as pulmonary edema associated with severe ventricular dysfunction at 7 months of age, when the mortality rate is 50.0% 12,17 . The gene inactivation of the α 2A and α 2C adrenergic receptors leads to an increase in the release of circulating noradrenaline 18,19 . Therefore, the HF observed in this model results from sympathetic nervous system hyperactivity.…”