Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans.

Area of Science:

• Pharmacogenomics
• Cardiovascular Physiology
• Molecular Biology

Background:

• Altered beta-adrenergic regulation is linked to hypertension.
• Beta-2 adrenoceptor gene (ADRB2) polymorphism may explain variable vascular responses to beta-agonists like isoproterenol.
• The Gln27 variant of ADRB2 might lead to reduced vascular reactivity due to receptor downregulation.

Purpose of the Study:

• To investigate the impact of ADRB2 polymorphisms (Gln27 and Arg16) on vascular reactivity to isoproterenol in normotensive individuals.
• To determine if specific ADRB2 genotypes influence forearm blood flow regulation.

Main Methods:

• Screening of 127 normotensive subjects for ADRB2 polymorphisms (Gln27 and Arg16).
• Brachial artery infusions of isoproterenol (1-300 ng/min) and measurement of forearm blood flow via plethysmography.
• Local intra-venous infusions of isoproterenol in pre-constricted dorsal hand veins.

Main Results:

• Subjects with the Gln27 ADRB2 variant exhibited lower baseline blood flow and attenuated forearm blood flow response to isoproterenol compared to Glu27 homozygotes.
• The Arg16 ADRB2 variant was associated with lower basal blood flow and reduced forearm blood flow response, particularly in veins.
• Vascular responses to isoproterenol were significantly influenced by both Gln27 and Arg16 ADRB2 genotypes in forearm resistance and capacitance vessels.

Conclusions:

• Beta-2 adrenoceptor genotype significantly determines vascular responses to isoproterenol in forearm vessels.
• ADRB2 polymorphisms may play a role in the development of hypertension, warranting further investigation.