α-adrenoreceptors in hypertension

The most important central autonomic pathways in the control of arterial blood pressure are the baroreceptor reflex pathway and descending pathways from the hypothalamus. Central neurotransmitters in these pathways are L-glutamate, substance P, norepinephrine (NE). γ-aminobutyric acid, epinephrine, neuropeptide Y, and acetylcholine. At peripheral autonomic neurovascular junctions, there are prejunctional α₂- and dopamine-2 receptors, which inhibit NE release, and β- and serotonin receptors, which stimulate NE release. Postjunctional α₁-receptors open sodium channels, open calcium channels via phosphoinositol release, and release intracytoplasmic calcium. Postjunctional α₂-receptors, which are extrasynaptic, inhibit adenylate cyclase and also open calcium channels. In animal models of hypertension, changes in α-receptor density have been reported. In spontaneously hypertensive rats, increased renal β- and α₂-receptors, respectively, may enhance renin release and cause sodium and water retention. In experimental (renovascular) hypertension, vascular postsynaptic (vasoconstrictor) α₁- and α₂-receptors are increased. In both models of hypertension, β-receptors are down-regulated. Selective α₁-antagonists, such as indoramin and prazosin, decrease arterial blood pressure by postsynaptic α₁-blockade; α₂-receptor inhibition of NE release is unaffected so that there is no β-receptor-mediated tachycardia.