Selective α 1-blockers are used in the treatment of primary hypertension, although their use is not as widespread as other antihypertensive drugs. They are even more effective under conditions of elevated sympathetic activity (e.g., during stress) or during pathologic increases in circulating catecholamines caused by an adrenal gland tumor ( pheochromocytoma). Because most blood vessels have some degree of sympathetic tone under basal conditions, these drugs are effective dilators. Furthermore, blocking α 2-prejunctional adrenoceptors in the heart can lead to increases in heart rate and contractility due to the enhanced release of norepinephrine that binds to beta 1-adrenoceptors.Īlpha-blockers dilate both arteries and veins because both vessel types are innervated by sympathetic adrenergic nerves however, the vasodilator effect is more pronounced in the arterial resistance vessels. Non-selective α 1 and α 2-adrenoceptor antagonists block postjunctional α 1 and α 2-adrenoceptors, which causes vasodilation however, the blocking of prejunctional α 2-adrenoceptors leads to increased release of norepinephrine, which attenuates the effectiveness of the α 1 and α 2-postjunctional adrenoceptor blockade. Α 1-adrenoceptor antagonists cause vasodilation by blocking the binding of norepinephrine to the smooth muscle receptors. There are also α 2-adrenoceptors located on the sympathetic nerve terminals that inhibit the release of norepinephrine and therefore act as a negative feedback mechanism for modulating the release of norepinephrine. These receptors are linked to Gi-proteins, and binding of an alpha-agonist to these receptors decreases intracellular cAMP, which causes smooth muscle contraction. Depending on the tissue and type of vessel, there are also α 2-adrenoceptors found on the smooth muscle. The α 1-adrenoceptors are the predominant α-receptors located on vascular smooth muscle. These receptors are linked to Gq-proteins that activate smooth muscle contraction through the IP 3 signal transduction pathway. Vascular smooth muscle has two types of alpha-adrenoceptors: alpha 1 (α 1) and alpha 2 (α 2). Some alpha-blockers are non-competitive (e.g., phenoxybenzamine), which greatly prolongs their action because of their strong binding to the receptor. Therefore, sometimes these drugs are referred to as sympatholytics because they antagonize sympathetic activity. Most of these drugs act as competitive antagonists to the binding of norepinephrine that is released by sympathetic nerves synapsing on smooth muscle. These drugs block the effect of sympathetic nerves on blood vessels by binding to alpha-adrenoceptors located on the vascular smooth muscle.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |