A Review of Why and How We May Use β-Blockers in Congestive Heart Failure: Long-term sympathetic stimulation
With long-term sympathetic stimulation, the ability of noradrenergic sympathetic nerve endings of the heart to synthesize norepinephrine is attenuated. In animals, sympathetic blockade can restore the ability to make norepinephrine.
Upregulation and Downregulation of β-Receptors
Repeated or prolonged exposure to β-agonists causes the β-receptors to become desensitized by chemical uncoupling to binding proteins. Uncoupling makes β-receptors nonreactive when tested by the chemical reaction used to mark their presence. P-Receptor density, ie, the total number of β-receptors, can also be decreased by prolonged exposure to the norepinephrine caused by heart failure and is independent of the decreased sensitivity caused by uncoupling. The decrease in β-receptor density is what is usually meant by downregulation. However, a decreased β-receptor sensitivity as well as a decrease in number is often included in the term “downregulation.” Sackner-Bernstein and colleagues did a study that suggested that β-receptor uncoupling is the more important physiologic response to sympathetic activation. buy zyrtec online
Antibodies to β1-receptors have been found in subjects with progressive familial cardiomyopathy, and β-blockers may attenuate their effect, which could result in upregulation. In one study of 32 patients with CHF of various etiologies, the serum of 15 of 18 idiopathic DCM patients and 7 of 15 other types of CHF patients prevented in vitro binding of the β-blocker alprenolol to cardiac myocyte β-receptors. None of the healthy control serum caused binding inhibition. Preincubation of the positive serum samples with antihuman 7-globulin prevented binding inhibition. These β-receptor responses have been found to depend on some unknown serum factor that is perhaps an antibody. Upregulation may mean a decrease in this serum factor, and β-blockade may cause a decrease in this serum factor. Therefore, the tests of upregulation or downregulation of β-receptors may only be tests for how well the β-receptors respond to the serum factor and not an actual change in the number of β-receptors.