The pharmacological basis for the use of alpha 1‐adrenoceptor antagonists in the treatment of essential hypertension.

Abstract

Effective preventive antihypertensive therapy is more likely to be achieved with drugs whose mechanisms and sites of action are congruent with the underlying aetiology and pathophysiology than by drugs that lower blood pressure by means unrelated to the process of hypertension. A vast amount of experimental and clinical data exist in favour of the neurogenic hypothesis. Thus hyperactivity of the sympathetic nervous system plays a major role in the pathogenesis and maintenance of essential hypertension and a generalized increase in peripheral vascular resistance is the fundamental haemodynamic abnormality. Reduction in increased sympathetic activity by alpha‐adrenoceptor blockade was one of the earliest pharmacological attempts to treat hypertension. However the discovery of postjunctional alpha 1‐ adrenoceptor antagonists represented the crucially important step in the development of agents to combat specifically adrenergic predominance in essential hypertension. This has yielded antihypertensive drugs of high specificity which preserve feedback control of transmitter noradrenaline release and consequently cause minimal reflex activation of the sympathetic nervous system. These properties have important clinical implications with respect to the therapeutic application of alpha 1‐adrenoceptor antagonists in the treatment of hypertension, and in addition explain why the clinical expectations of the early alpha‐adrenoceptor antagonists remained unfulfilled. Alpha 1‐Adrenoceptor antagonists represent an attractive alternative choice for initial therapy in all grades of hypertension.

Paracrine control of vascular innervation in health and disease

“…2004), and a causal relationship is suggested by the well‐documented anti‐hypertensive efficacy of sympatholytic drugs, e.g. α‐ and β‐adrenoreceptor blockers (Goldstein 1983, Davey 1986, 1987, Anderson et al. 1989, Guyenet 2006, Grassi et al.…”

Alpha‐adrenergic blockers: Mechanism of action, blood pressure control, and effects on lipoprotein metabolism

“…A number of mechanisms have been proposed to explain the influence of adrenergic antagonists on lipid metabolism. 3 1 The first involves adrenergic modulation of lipoprotein lipase, a key enzyme involved in the breakdown of triglycerides into free fatty acids, via constriction of the precapillary sphincter tone in microcirculatory vessels. Blockade of the a-adrenergic pathway leads to increased capillary flow and greater availability of lipoprotein lipase, which ultimately results in decreased plasma levels of triglycerides and triglyceride-rich lipoproteins.…”