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  • Title: Alpha 2-adrenergic receptors and calcium: alpha 2-receptor blockade in vascular smooth muscle as an approach to the treatment of hypertension.
    Author: Lee JY, DeBernardis JF.
    Journal: Methods Find Exp Clin Pharmacol; 1990 Apr; 12(3):213-25. PubMed ID: 1972206.
    Abstract:
    Vascular contractile effects of postsynaptic alpha 2-adrenergic receptor stimulation are believed to involve transmembrane calcium influx. Although the current knowledge of the alpha 2-receptor response coupling of vascular smooth muscle contractions is still limited, the fundamental mechanism(s) may involve the extracellular calcium utilization process. This is mediated via the alpha 2-receptor operated calcium channel, which can be pharmacologically distinguished from that mediated via the potential-dependent calcium channel. Therefore, vascular selective alpha 2-antagonists may produce vasorelaxation via a calcium inhibitory action that is different from that of the typical calcium channel blockers. The literature on the in vitro isolated vascular tissue models has been reviewed with emphasis on the methodology for study of alpha 2-antagonist-induced vascular relaxation via selective blockade of the alpha 2-receptor-operated calcium channel. The alpha 2-adrenergic receptors, like alpha 1-receptors on vascular smooth muscle, serve an important role in the control of the arterial, as well as the venous tone in experimental animals and humans in relationship to sympathetic and humoral adrenergic activation of the cardiovascular system. Of particular importance is the possibility that alterations in vascular control of alpha 2-adrenergic mechanisms may lead to increased intracellular free calcium concentrations, thereby causing elevated vascular resistance and high blood pressure. This view is consistent with the long held concept that disturbances of cellular calcium metabolism play a primary role in the pathogenesis of various forms of hypertension. Consequently, selective blockade of vascular alpha 2-adrenergic receptors would be a feasible approach for antihypertensive therapy. This type of antihypertensive agent would be expected to exhibit fewer side effects with efficacy, directed towards the etiology of hypertension.
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