Altered Neural and Vascular Mechanisms in Hypertension

Abstract

Essential hypertension is a multifactorial disorder which belongs to the main risk factors responsible for renal and cardiovascular complications. This review is focused on the experimental research of neural and vascular mechanisms involved in the high blood pressure control. The attention is paid to the abnormalities in the regulation of sympathetic nervous system activity and adrenoceptor alterations as well as the changes of membrane and intracellular processes in the vascular smooth muscle cells of spontaneously hypertensive rats. These abnormalities lead to increased vascular tone arising from altered regulation of calcium influx through L-VDCC channels, which has a crucial role for excitation-contraction coupling, as well as for so-called “calcium sensitization” mediated by the RhoA/Rho-kinase pathway. Regulation of both pathways is dependent on the complex interplay of various vasodilator and vasoconstrictor stimuli. Two major antagonistic players in the regulation of blood pressure, i.e. sympathetic nervous system (by stimulation of adrenoceptors coupled to stimulatory and inhibitory G proteins) and nitric oxide (by cGMP signaling pathway), elicit their actions via the control of calcium influx through L-VDCC. However, L-type calcium current can also be regulated by the changes in membrane potential elicited by the activation of potassium channels, the impaired function of which was detected in hypertensive animals. The dominant role of enhanced calcium influx in the pathogenesis of high blood pressure of genetically hypertensive animals is confirmed not only by therapeutic efficacy of calcium antagonists but especially by the absence of hypertension in animals in which L-type calcium current was diminished by pertussis toxin-induced inactivation of inhibitory G proteins. Although there is considerable information on the complex neural and vascular alterations in rats with established hypertension, the detailed description of their appearance during the induction of hypertension is still missing.

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“…Vascular smooth muscle cells (VMC) express b-receptors for vasodilation and a 1 -/a 2 -adrenoceptors for vasoconstriction. Activation of endothelial a 2 -adrenoceptor by the release of NE from the sympathetic nerve terminals (which terminate in medial VMC layer) releases NO causing endothelium-dependent vasodilation (Guimarães & Moura, 2001;Pintérová et al, 2011). Endothelial-derived signals and physical factors, such as hypoxia and stretching, stimulate vascular sensory afferents, and resultant activity in the efferent vasomotor nerve causes the release of catecholamines from the varicosities (Stohler, 2002).…”

Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective

“…K ir are specifically inhibited by Ba +2 and Cs + , whereas some of the other K + channel inhibitors such as 4‐AP or TEA have little effect on K ir . In small‐resistance arteries, such as the brain and coronary arteries, K ir is activated by an increase of 15 m m in the extracellular concentration .…”

“…K + conductance plays a pivotal role in the regulation of contractile function in arterial VSM. Disorders in the functions or activities of the K + channels may be associated with the pathophysiological mechanism of hypertension leading to vasoconstriction . K + currents in VSMCs are one of the most effective factors in preserving membrane stability, they can suppress the membrane excitability, so less K + current may occur in the hypertension disease than in the normotensive state .…”

A monoclonal antibody derived by inoculation of human umbilical vein endothelial cells is a potential inhibitor of acetylcholine receptor-linked vasorelaxation

“…The NO diffuses into SMC layers and activates guanylate cyclase, which induces the elevation of cyclic guanosine monophosphate to elicit vascular SMC relaxation through multiple mechanisms (Omori and Kotera 2007). These responses suggest that NO plays an essential role in the regulation of vascular contractility (Pintérová et al 2011). Human body is exposed to various external stimuli that change blood flow and blood pressure, which are closely associated with NO (Furchgott 1983).…”