Rostral Ventrolateral Medulla

Bergamaschi, Cássia Toledo; Campos, Rui; Lopes, Oswaldo Ubrı́aco

doi:10.1161/01.hyp.34.4.744

Cited by 40 publications

(14 citation statements)

References 37 publications

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“…These results suggest that increased RSNA contributes to hypertension induced by chronic NOS inhibition and that activation of the renin-angiotensin system in the NTS is involved, at least in part, in the increased RSNA via AT 1 receptors (29). The rostral ventrolateral medulla (RVLM), the vasomotor center, is also activated in this model of hypertension, suggesting enhanced central sympathetic outflow (9). Pharmacological inhibition of NOS evoked by N G -monomethyl-L-arginine (L-NMMA) or L-NAME also induces large increases in blood pressure that are partially sympathetically mediated in humans (109).…”

Section: No In the Brainmentioning

confidence: 68%

“…Esler (30) reported that the sympathetic nervous system is activated in ϳ50% of patients with hypertension, particularly in patients with essential hypertension. Central sympathetic outflow is determined by several important nuclei and their circuits in the central nervous system (CNS) (9,81). These pathways involve many neurotransmitters and neuromodulators (16,25,38,99).…”

mentioning

confidence: 99%

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Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

Hirooka

Kishi

Sakai

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

109

108

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Hirooka Y, Kishi T, Sakai K, Takeshita A, Sunagawa K. Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension. Am J Physiol Regul Integr Comp Physiol 300: R818-R826, 2011. First published February 2, 2011 doi:10.1152/ajpregu.00426.2010 and reactive oxygen species (ROS) play important roles in blood pressure regulation via the modulation of the autonomic nervous system, particularly in the central nervous system (CNS). In general, accumulating evidence suggests that NO inhibits, but ROS activates, the sympathetic nervous system. NO and ROS, however, interact with each other. Our consecutive studies and those of others strongly indicate that an imbalance between NO bioavailability and ROS generation in the CNS, including the brain stem, activates the sympathetic nervous system, and this mechanism is involved in the pathogenesis of neurogenic aspects of hypertension. In this review, we focus on the role of NO and ROS in the regulation of the sympathetic nervous system within the brain stem and subsequent cardiovascular control. Multiple mechanisms are proposed, including modulation of neurotransmitter release, inhibition of receptors, and alterations of intracellular signaling pathways. Together, the evidence indicates that an imbalance of NO and ROS in the CNS plays a pivotal role in the pathogenesis of hypertension. blood pressure; sympathetic nervous system; central nervous system; nitric oxide; oxidative stress ACTIVATION OF THE SYMPATHETIC nervous system is critically involved in the pathogenesis of hypertension, from initial occurrence to the development of target organ damage, such as heart failure, stroke, and renal failure (35,36). The importance of the effects of the renin-angiotensin system on the sympathetic nervous system in the pathogenesis of hypertension is recently highlighted (30,31). This is not surprising because both the autonomic nervous system and hormonal factors are the major regulators of blood pressure; therefore, abnormalities of either system are likely to be involved in the pathogenesis of essential hypertension (30,31,37). Esler (30) reported that the sympathetic nervous system is activated in ϳ50% of patients with hypertension, particularly in patients with essential hypertension. Central sympathetic outflow is determined by several important nuclei and their circuits in the central nervous system (CNS) (9, 81). These pathways involve many neurotransmitters and neuromodulators (16,25,38,99). In particular, the brain stem circuitry is now considered crucial for the pathogenesis of hypertension, including both excitatory and inhibitory inputs from the supramedullary nuclei and the baroreceptors (16,25,38,100,115). In this review, we focus on the role of nitric oxide (NO) and reactive oxygen species (ROS) in the brain stem as factors constituting the neural mechanisms of hypertension. Because of the close relationship between NO and ROS, we discuss the individual roles of NO and ROS in the brain stem i...

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Section: No In the Brainmentioning

confidence: 68%

mentioning

confidence: 99%

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

Hirooka

Kishi

Sakai

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

109

108

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“…The rostral ventrolateral medulla (RVLM) neurons are activated in rats with chronic NO synthase inhibition. 26 Intracisternal infusion of a drug might affect neurons not only in the NTS but also in the rostral ventrolateral medulla. 27 Therefore, intracisternal infusion of Y-27632 might also alter neuronal activity in areas other than the NTS, such as the rostral ventrolateral medulla in L-NAME-treated rats.…”

Section: Discussionmentioning

confidence: 99%

Rho/Rho-Kinase Pathway in the Brainstem Contributes to Hypertension Caused by Chronic Nitric Oxide Synthase Inhibition

et al. 2004

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Abstract-Central nervous system mechanisms are involved in hypertension caused by chronic inhibition of nitric oxide (NO) synthesis. Chronic inhibition of NO synthesis might also activate the Rho/Rho-kinase pathway in the vasculature.We recently demonstrated that activation of the Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) contributes to hypertensive mechanisms in spontaneously hypertensive rats. The aim of the present study was to determine whether activation of this pathway also contributes to neurogenic hypertensive mechanisms caused by chronic NO synthesis inhibition. The NO synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME) was administered to Wistar-Kyoto rats in their drinking water (1 mg/mL) for 2 weeks. Bilateral microinjection of Y-27632, a specific Rho-kinase inhibitor, into the NTS elicited decreases in arterial pressure, heart rate, and renal sympathetic nerve activity in control rats and L-NAME-treated rats. The magnitude of the decrease, however, was significantly greater in L-NAME-treated than in control rats. In another group of rats, the specific Rho-kinase inhibitor, Y-27632, was administered intracisternally for 2 weeks with a mini-osmotic pump from the beginning of treatment with L-NAME. Y-27632 co-treatment significantly attenuated the increase in arterial pressure. Furthermore, the expression level of membranous RhoA and phosphorylation of the target proteins of Rho-kinase, the ERM (ezrin, radixin, moesin) family members, was significantly greater in L-NAME-treated rats than in control rats. These results indicate that activation of the Rho/Rho-kinase pathway in the NTS contributes to neurogenic hypertension caused by chronic NO synthase inhibition. Key Words: nitric oxide Ⅲ blood pressure Ⅲ sympathetic nervous system Ⅲ hypertension Ⅲ brain I nhibition of nitric oxide (NO) synthesis produces hypertension in many species. 1,2 Although this hypertension was initially attributed to the inhibition of endothelial NO synthesis, numerous studies suggest that inhibition of neuronal NO also plays an important role in blood pressure regulation. [3][4][5][6][7] A previous study demonstrated that increased sympathetic nerve activity plays a role in hypertension caused by chronic NO synthesis inhibition, and activation of the renin-angiotensin system in the nucleus tractus solitarii (NTS) of the brainstem via angiotensin II type 1 receptors is involved. 8 Chronic inhibition of NO synthesis might activate the Rho/ Rho-kinase pathway in the cardiac tissues or vasculature. 9,10 The Rho/Rho-kinase pathway regulates the phosphorylation state of myosin light chains and contributes to smooth muscle contraction. 11 Y-27632, a specific Rho-kinase inhibitor, dramatically reduces blood pressure in rat models of hypertension. 12 In addition, Rho-kinase activity is augmented in hypertensive blood vessels 13 and inhibition of Rho-kinase induces preferential forearm vasodilatation in hypertensive patients, but not in normal subjects. 14 Thus, the Rho/Rhokinase pathway plays an important r...

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“…In addition, the potentiation of vasoconstrictor responses to ANG II, which constitutes the important element underlying the slow responses, was also seen in isolated (pump perfused) mesenteric vascular bed (1). It will be impossible here to review the vast amount of data on the controversial aspects of the participation of the central nervous system in angiotensin-induced hypertension (18,37,46,80,120). However, results of several studies reviewed by Krukoff (80) and Patel et al (120) show that the synthesis of NO decreases sympathetic output to periphery in several autonomic nucleus.…”

Section: Effects Of Ang II Oxst and No On The Regulation Of Sympathmentioning

confidence: 99%

Role of oxidative stress in angiotensin-induced hypertension

Reckelhoff

Romero

2003

American Journal of Physiology-Regulatory, Integrative and Comp

167

133

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Reckelhoff, Jane F., and J. Carlos Romero. Role of oxidative stress in angiotensin-induced hypertension. Am J Physiol Regul Integr Comp Physiol 284: R893-R912, 2003; 10.1152/ajpregu.00491.2002.-Infusion of ANG II at a rate not sufficient to evoke an immediate vasoconstrictor response, produces a slow increase in blood pressure. Circulating levels of ANG II may be within ranges found in normotensive individuals, although inappropriately high with respect to sodium intake. When ANG II levels are dissociated from sodium levels, oxidative stress (OXST) occurs, which can increase blood pressure by several mechanisms. These include inadequate production or reduction of bioavailability of nitric oxide, alterations in metabolism of arachidonic acid, resulting in an increase in vasoconstrictors and decrease in vasodilators, and upregulation of endothelin. This cascade of events appears to be linked, because ANG II hypertension can be blocked by inhibition of any factor located distally, blockade of ANG II, OXST, or endothelin. Such characteristics are shared by other models of hypertension, such as essential hypertension, hypertension induced by reduction in renal mass, and renovascular hypertension. Thus these findings are clinically important because they reveal 1) uncoupling between ANG II and sodium, which can trigger pathological conditions; 2) the various OXST mechanisms that may be involved in hypertension; and 3) therapeutic interventions for hypertension developed with the knowledge of the cascade involving OXST.isoprostanes; endothelin; spontaneous hypertension; renovascular hypertension; sodium balance THREE DECADES AGO, the production of free radicals was thought to be the result of severe injuries or pathological insults such as those resulting from exposure to high-energy radiation or toxins such as carbon tetrachloride (127). However, in 1968, the discovery of superoxide dismutase (SOD) by McCord and Fridovich (96) strongly suggested that all aerobically metabolizing cells are capable of producing superoxide ions, which could play a role in normal metabolic processes. The concomitant discovery of the biology of nitric oxide (NO) strongly suggested that free radicals could constitute the basis of metabolic regulation (67,90,118). One of the first findings supporting such a notion was the demonstration that the inhibition of the synthesis of NO produced by the administration of an NO synthesis competitor, such as N -monomethyl-Larginine] or N G -nitro-L-arginine methyl ester (L-NAME), produced a marked vasoconstriction (13,136,173), sodium retention (82, 83), and thereby a sustained increase in mean arterial pressure (MAP) (13,82,83,136,173). The identification of a specific pathological situation in humans, where a decrease of NO may end up in an elevation of blood pressure was thought to be linked to endothelial dysfunction (105), such as those involved in aging, arteriosclerosis, etc., but the specific metabolic alterations involved in this process were poorly understood. However, the relationship betw...

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Rostral Ventrolateral Medulla

Cited by 40 publications

References 37 publications

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension

Rho/Rho-Kinase Pathway in the Brainstem Contributes to Hypertension Caused by Chronic Nitric Oxide Synthase Inhibition

Role of oxidative stress in angiotensin-induced hypertension

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