24 Effect of antihypertensive treatment on increased (??2-adrenoceptor density in patients with essential hypertension

β2-Adrenergic receptor polymorphisms and treatment-induced regression of left ventricular hypertrophy in hypertension

“…In hypertension the relative abundances of β 1 and β 2 AR are inverted. In experimental 15 and human hypertension 14 there is a down‐regulation of β 1 AR and an up‐regulation of the β 2 AR subtype. These modifications have been related to alterations in the sympathetic discharge, which can be corrected by ACE inhibitors 15 .…”

“…Under experimental conditions, transgenic overexpression of α 1B AR 9 and β 1 AR 10 and high levels of β 2 AR 11 in the heart, as well as long‐term stimulation of αAR 12 or βAR 13 by means of selective drugs, cause enlargement of cardiac size. Under physiologic conditions, β 2 AR in the heart is relatively less abundant, but in hypertension, as well as in other cardiovascular conditions, this receptor is up‐regulated during concomitant down‐regulation of β 1 AR 14 , 15 . β 2 AR is also polymorphic, with 3 variants in particular that cause changes in the amino acid sequence and alteration in regulation of signal transduction.…”

“…As a consequence, in Glu27 β 2 AR patients, drugs that cause both BP normalization and a reduction in sympathetic activation may provide a further advantage with regard to LVH regression. Therefore we investigated whether the presence of the Glu27 β 2 AR variant in humans is associated with a different degree of reduction in LVMi when BP is reduced with β 1 ‐blockers, which are unable to completely block β 2 AR, 28 rather than with angiotensin‐converting enzyme (ACE) inhibitors, which in hypertension reduce the whole sympathetic discharge 14 , 29 …”

“…Under physiologic conditions, ␤ 2 AR in the heart is relatively less abundant, but in hypertension, as well as in other cardiovascular conditions, this receptor is up-regulated during concomitant down-regulation of ␤ 1 AR. 14,15 ␤ 2 AR is also polymorphic, with 3 variants in particular that cause changes in the amino acid sequence and alteration in regulation of signal transduction. In particular, Arg16Gly is associated with increased agonist-induced down-regulation (though recent data challenge this assertion 16 ), Gln27Glu leads to resistance to downregulation, and Thr164Ile causes receptor uncoupling from the G protein.…”

“…Therefore we investigated whether the presence of the Glu27 ␤ 2 AR variant in humans is associated with a different degree of reduction in LVMi when BP is reduced with ␤ 1 -blockers, which are unable to completely block ␤ 2 AR, 28 rather than with angiotensin-converting enzyme (ACE) inhibitors, which in hypertension reduce the whole sympathetic discharge. 14,29 Central to this hypothesis are the functional changes caused by Glu27 polymorphism in terms of regulation of ␤ 2 AR signaling. So far, the impact of the Glu27 ␤ 2 AR variant on intracellular signal transduction is known for the production of cyclic adenosine monophosphate (cAMP), 26 which relates to short-term functional changes rather than to the structural modification in cardiomyocytes.…”