Aj Receptor Antagonists Blockade of ax adrenergic receptors inhibits vasoconstriction induced by endogenous catecholamines; vasodilation may occur in both arteriolar resistance vessels and veins. The result is a fall in blood pressure due to decreased peripheral resistance; the magnitude of such effects depends on the activity of the sympathetic nervous system, is less in supine than in upright subjects, and is enhanced by hypovolemia. For most a receptor antagonists, the fall in blood pressure is opposed by baroreceptor reflexes that cause increases in heart rate and cardiac output, as well as fluid retention. These compensatory reflexes are exaggerated if the antagonist also blocks a2 receptors on peripheral sympathetic nerve endings, leading to enhanced release of NE and increased stimulation of postsynaptic b1 receptors in the heart and on juxtaglomerular cells. Since blockade of a1 receptors inhibits vasoconstriction, pressor responses to Epi may be transformed to vasodepressor effects ("epinephrine reversal") due to unopposed stimulation of b2 receptors in the vasculature with resultant vasodilation.
a2 Adrenergic Receptor Antagonists Activation of a2 receptors in the pontomedullary region of the CNS inhibits sympathetic nervous system activity and leads to a fall in blood pressure; these receptors are a site of action for drugs such as clonidine. Activation of presynaptic a2 receptors inhibits the release of NE and cotransmitters from peripheral sympathetic nerve endings. Thus, blockade of peripheral a2 receptors with selective antagonists such as yohimbine increases sympathetic outflow and potentiates the NE release, leading to activation of a1 and b1 receptors in the heart and peripheral vasculature with a consequent rise in blood pressure. Antagonists that simultaneously block a1 and a2 receptors cause similar effects on sympathetic outflow and NE release, but the net increase in blood pressure is prevented by inhibition of vasoconstriction (a1 blockade).
The physiological role of vascular a2 receptors in the regulation of blood flow within various vascular beds is uncertain. Vacular a2 receptors probably are preferentially stimulated by circulating catecholamines, whereas a1 receptors are activated by NE released from sympathetic nerves.
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