Resting sympathetic nerve activity is related to age, sex and arterial pressure but not to α2-adrenergic receptor subtype.
OBJECTIVE
Sympathetic nerve hyperactivity has been associated with hypertension and heart failure and their cardiovascular complications. The α2-adrenergic receptors have been proposed to play a prominent role in the control of sympathetic neural output, and their malfunction to constitute a potential central mechanism for sympathetic hyperactivity of essential hypertension. Reports on the relationship between variant alleles of α2-adrenergic receptor subtypes and sympathetic drive or its effects, however, have not been consistent. Therefore, this study was planned to test the hypothesis that variant alleles of subtypes of α2-adrenergic receptors are associated with raised muscle sympathetic nerve activity (MSNA) in man.


METHODS
One hundred and seventy-two individuals, with a wide range of arterial pressure, were prospectively examined. Resting MSNA was quantified from multiunit bursts and from single units, and α2-adrenergic receptor subtypes were genotyped from DNA extracted from leucocytes and quantified by spectrophotometry.


RESULTS
No significant relationships between variant alleles of any of the α2A, α2B or α2C subtypes and raised muscle sympathetic activity were found. In contrast, MSNA showed a marked significant curvilinear relationship with age and systolic pressure; sex had a small but statistically significant effect. The α2-adrenergic receptor variants had a similar frequency when hypertensive and normotensive individuals were compared.


CONCLUSIONS
Variant alleles of three α2-adrenergic receptor subtypes were not related to resting muscle sympathetic nerve hyperactivity, indicating that their functional differences shown in vitro are not reflected in sympathetic activity in man. Age had a marked effect likely influencing arterial pressure through sympathetic activity.
Maqbool
Azhar
A
Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics, Leeds, UK.
West
Robert M
RM
Galloway
Stacey L
SL
Drinkhill
Mark J
MJ
Mary
David A S G
DA
Greenwood
John P
JP
Ball
Stephen G
SG
D000375:Aging / Q000502:physiology*; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation; D011446:Prospective Studies; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D012146:Rest / Q000502:physiology*; D012727:Sex Characteristics; D013564:Sympathetic Nervous System / Q000502:physiology*
D018341:Receptors, Adrenergic, alpha-2