Centrally acting antihypertensive drugs: Re-emergence of sympathetic inhibition in the treatment of hypertension

Abstract

Central regulation of the sympathetic nervous system plays an important role in the maintenance of blood pressure. In a subset of patients with essential hypertension, sympathetic activation may contribute to the development and maintenance of hypertension. Unlike the first generation of centrally active antihypertensive drugs, the second generation may be superior because of its selectivity to I1-imidazoline receptor and selective binding to the vasomotor center. Lack of a2 effects differentiates moxonidine from clonidine with respect to monoxidine"s superior side-effect profile (little or no sedation or dry mouth). Clinical trials show that moxonidine is as effective as angiotensin-converting enzyme inhibitors (eg, enalapril and captopril), b-blockers (e.g., atenolol), calcium-channel blockers (e.g., long-acting nifedipine), and diuretics (eg, hydrochlorothiazide) in lowering blood pressure and that it has superior tolerability. Thus, central modulation of the sympathetic nervous system has re-emerged as an exciting target for blood pressure reduction. Given the multiple adverse effects of sympathetic stimulation in various disease processes, including congestive heart failure, moxonidine may be the next therapeutic option for the management of hypertension and the prevention of target organ dysfunction.

Effect of the C825T polymorphism of the G protein β3 subunit on the systolic blood pressure–lowering effect of clonidine in young, healthy male subjects

“…Clonidine exerts its BP-lowering effect via central sympathomimetic inhibition. 25,26 This sympatholytic mode of action has been confirmed in humans by direct microneurographic recordings from sympathetic fibers of the peroneal nerve. 27,28 The hemodynamic effects of clonidine observed in our study are entirely consistent with the established concept of the sympatholytic mode of action of clonidine.…”

“…In animal experiments, 13 as well as clinical pharmacologic studies in humans, 24 the BP reduction in response to administration of clonidine can be attenuated by pretreatment with α 2 ‐adrenergic receptor antagonists, supporting the key role of stimulation of α 2 ‐adrenergic receptors in the hypotensive effect of clonidine. Clonidine exerts its BP‐lowering effect via central sympathomimetic inhibition 25 , 26 . This sympatholytic mode of action has been confirmed in humans by direct microneurographic recordings from sympathetic fibers of the peroneal nerve 27 , 28 .…”

Changes of imidazoline receptors in spontaneously hypertensive rats

“…In recent studies agmatine has been used as both agonist and antagonist at the imidazoline receptors, but can bind to imidazoline receptors/recognition sites without inducing an effect (Molderings & Haenisch 2012). The antihypertensive effects of moxonidine are also thought to occur through activation of I 1 -imidazoline receptors, which have been reported to lower sympathetic nervous tone (Benedict 1999). The previous studies showed that intravenous application of agmatine decreased arterial pressure and sympathetic nerve activity due to blockade of transmission through sympathetic ganglia (Sun et al 1995) and inhibition of carotid baroreflex in anaesthetized rats (Qin & He 2001).…”

Renal denervation in patient with resistant hypertension: A case report

“…Spoznaja da lekovi koji deluju kao centralni simpatikolitički agensi, kao što su klonidin i moksonidin, značajno redukuju KP, bila je osnov antihipertenzivne terapije sredinom 70-ih godina prošlog veka. 36 Primena ovih lekova bila je udružena sa neželjenim efektima, posebno posturalnom hipotenzijom i sinkopama, te su svoje mesto prepustili savremenim predstavnicima antihipertenzivnih lekova.…”