Nonrespiratory Effects
Variability in β-adrenergic receptor response in the vasculature: Role of receptor polymorphism,☆☆

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Abstract

β-adrenergic receptors (βARs) are important in determining vascular tone. Stimulation of β2ARs in the vasculature produces vasodilatation, which acts to counteract the vasoconstriction produced by endogenous sympathetic agonists. Impaired vasodilatation occurs in human hypertension and in Blacks. It is now clear that receptor polymorphism may contribute to some of the variability seen in vascular response. β2AR haplotypes determine the desensitization response to chronic agonist exposure in vivo and result in altered vasodilatory responses. (J Allergy Clin Immunol 2002;110:S318-21.)

Section snippets

βAR-mediated vasodilatation in hypertension

The study of βAR response in the vasculature is difficult because of the complicating effects of cardiovascular reflexes, which are stimulated by changes in vascular tone produced by the administration of vasoactive agents. For that reason vascular responses are best studied after direct infusion of agonists into the vascular bed of interest at doses insufficient to produce systemic effects. By using the technique of infusion of isoproterenol directly into the brachial artery of persons with

βAR-mediated vasodilatation in different ethnic groups

There are marked racial differences in the frequency and severity of hypertension, with blacks being at particular risk for hypertension. Even when matched with other ethnic groups for the severity of hypertension, blacks appear to have increased rates of morbidity associated with hypertension. The increase in blood pressure is associated with increased peripheral vascular resist-ance, which in turn reflects both impaired vasodilatation and increased vasoconstriction. By using the technique

Role of βAR polymorphisms in hypertension

The recognition that polymorphisms of the β2AR occur frequently led to the obvious question of whether such polymorphisms are associated with hypertension. In an Afro-Caribbean population, the Gly16 polymorphism was said to occur more frequently in hypertensive than in normotensive persons.4 However, the opposite was found in a German population, where Arg16 was more common in hypertensive persons.5 Because of the problem of linkage disequilibrium in these polymorphisms, we studied βAR

Conclusions

It appears that βAR polymorphism may be an important determinant of vascular response in humans. Further studies will be required to determine the contribution of these polymorphisms to vascular disease.

References (7)

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Supported by grants HL-56521, HL-65962, GM-31304 from National Institutes of Health.

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Reprint requests: Alastair J. J. Wood, MD, 550 RRB, 23rd Ave S at Pierce Ave, Nashville, TN 37232-6602; E-mail: [email protected] .

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