Role of endogenous nitric oxide in the nucleus tratus solitarii on baroreflex control of heart rate in spontaneously hypertensive rats

Pontieri, Vera; Venezuela, Maria Kelly; Scavone, Cristóforo; Michelini, Lisete Compagno

doi:10.1097/00004872-199816121-00021

Cited by 51 publications

(52 citation statements)

References 22 publications

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“…For instance, using in vivo unanesthetised decerebrate rats, elegant work from Paton's laboratory has shown that NO is able to act in the caudal NTS to attenuate the gain of the vagal component of the cardiac baroreflex (24,25). This is consistent with other in vivo evidence, which has shown that administration of NOS inhibitors in the NTS increased baroreflex sensitivity in both anesthetized and conscious animals (26,27). Conversely, Chowdhary and Townend (28) have reported that NO serves to inhibit central sympathetic outflow and studies by Di Paola et al (29) show that the neurotransmitter L-glutamate which promotes the release of NO from nitrergic neurones stimulates, rather than inhibits, baroreflex processing within the NTS.…”

Section: Discussionsupporting

confidence: 73%

Nitric Oxide Reduces Vagal Baroreflex Sensitivity in the Late Gestation Fetus

Thakor

Giussani

2009

Pediatr Res

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Goals to understand the etiology of essential hypertension have proposed that this problem arises, in part, because of changes within brainstem circuits involved in arterial blood pressure (ABP) control. It has been suggested that nitric oxide (NO) exerts inhibitory influences on the integration of afferent discharge from the arterial baroreceptors. This study tested the hypothesis that the inhibitory influence of NO on the arterial baroreflex is present in fetal life. Fetal baroreflex sensitivity was calculated in fetal sheep, before and during the NO-clamp; a technique that permits NO synthase (NOS) blockade with L-NAME while maintaining basal cardiovascular function with sodium nitroprusside. Under halothane anesthesia, five fetal sheep at 0.8 gestation were instrumented with vascular catheters. Five days later, fetuses received a range of bolus doses of phenylephrine (5-75 g I.A.) in randomized order either during saline or treatment with the NO clamp. Basal fetal ABP and heart rate before (50 Ϯ 4 mm Hg, 170 Ϯ 3 bpm) or during (51 Ϯ 4 mm Hg, 173 Ϯ 3 bpm) the NO-clamp were similar. The gradient of the pulse interval-ABP relationship was nearly doubled during NOS blockade (14.2 Ϯ 2.5 versus 7.8 Ϯ 1.6 ms/mm Hg). The data provide in vivo evidence that NO attenuates the sensitivity of the cardiac baroreflex during fetal life. (Pediatr Res 65: 269-273, 2009) T he arterial baroreflex plays an important role in maintaining cardiovascular homeostasis by continuously eliciting autonomic adjustments to maintain arterial blood pressure (ABP) within a narrow physiologic range. Baroreceptors are located in the carotid sinus and aortic arch, where they sense beat-by-beat changes in ABP. This information is relayed via primary afferent neurons to the brainstem, where the signal is processed and integrated. Compensatory adjustments in heart rate (HR) and vascular resistance, for any perturbations in ABP, are subsequently mediated via changes in efferent vagal and sympathetic outflow (1,2).Studies in both the adult and fetus have shown that there is an age-dependent fall in arterial baroreflex sensitivity (3,4). Accumulating evidence implicates nitric oxide (NO) in baroreflex pathways and its involvement in altering baroreflex sensitivity with ageing. For instance, NO synthase (NOS) immunoreactivity has been demonstrated in several locations of the baroreflex pathway, including the carotid sinus (5), the nucleus tractus solitarius (6), and the cardiac vagal and preganglionic sympathetic neurons (7,8). Further, the fall in baroreflex sensitivity with advancing age in conscious lambs is dependent on NO (9). However, it remains completely unknown whether the inhibitory influence on baroreflex sensitivity by NO is already present in fetal life. The present study tested the hypothesis that endogenous NO depresses baroreflex sensitivity during fetal life. Our own pilot studies and investigations by Schroder et al. (10) have shown that in fetal life, unloading of the arterial baroreceptors, for instance using bolus doses ...

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Section: Discussionsupporting

confidence: 73%

Nitric Oxide Reduces Vagal Baroreflex Sensitivity in the Late Gestation Fetus

Thakor

Giussani

2009

Pediatr Res

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“…2 NO-mediated actions in the CNS include central vascular regulation 27 and the baroreflex control of HR. 18 Antihypertensive activity, based on the facilitated release of GABA and glutamate in the CNS, and NO production are suggested to result in diminished transmission of sympathetic tone to the periphery. 27 However, no Bj-PRO-10c-induced changes of the sympathetic renal activity of SHRs were observed under anesthesia, and MAP of these animals also remained unchanged (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…17 Changes in neural-cardiovascular integration due to NO deficiency may be the main cause of autonomic abnormalities in several models of experimental hypertension 2 as a consequence of impaired arterial baroreflex. 3,18 As a result of augmented ASS activity, an enzyme also expressed in the CNS, 6 and central effects on the control of blood pressure 11,14 in the presence of Bj-PRO-10c, we expected to observe increased NO production in the brain and improved arterial baroreflex function in conscious SHRs. Therefore, this study was designed to examine the effects of Bj-PRO-10c on baroreflex sensitivity in SHRs and to elucidate involved mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Lameu

Pontieri

Guerreiro³

et al. 2010

Hypertens Res

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Baroreflex sensitivity is disturbed in many people with cardiovascular diseases such as hypertension. Brain deficiency of nitric oxide (NO), which is synthesized by NO synthase (NOS) in the citrulline-NO cycle (with argininosuccinate synthase (ASS) activity being the rate-limiting step), contributes to impaired baroreflex. We recently showed that a decapeptide isolated from Bothrops jararaca snake venom, denoted Bj-PRO-10c, exerts powerful and sustained antihypertensive activity. Bj-PRO-10c promoted vasodilatation dependent on the positive modulation of ASS activity and NO production in the endothelium, and also acted on the central nervous system, inducing the release of GABA and glutamate, two important neurotransmitters in the regulation of autonomic systems. We evaluated baroreflex function using the regression line obtained by the best-fit points of measured heart rate (HR) and mean arterial pressure (MAP) data from spontaneously hypertensive rats (SHRs) treated with Bj-PRO-10c. We also investigated molecular mechanisms involved in this effect, both in vitro and in vivo. Bj-PRO-10c mediated an increase in baroreflex sensitivity and a decrease in MAP and HR. The effects exerted by the peptide include an increase in the gene expression of endothelial NOS and ASS. Bj-PRO-10c-induced NO production depended on intracellular calcium fluxes and the activation of a G i/o -protein-coupled metabotropic receptor. Bj-PRO-10c induced NO production and the gene expression of ASS and endothelial NOS in the brains of SHRs, thereby improving baroreflex sensitivity. Bj-PRO-10c may reveal novel approaches for treating diseases with impaired baroreflex function. Hypertension Research (2010Research ( ) 33, 1283Research ( -1288 doi:10.1038/hr.2010 Keywords: argininosuccinate synthase; baroreflex sensitivity; Bothrops jararaca venom; nitric oxide; proline-rich oligopeptide INTRODUCTIONThe gaseous messenger NO is involved mainly in the regulation of local and systemic vascular resistance, sodium balance and, consequently, blood pressure control, 1 but it is also a signaling molecule and modulator of brain function. 2 Recent studies relate NO with central cardiovascular control through the regulation of the cardiac and vascular autonomic system via the modulation of the central sites of cardiovascular autonomic neural integration. 3,4 NO is generated in the citrulline-NO cycle by NO synthase (NOS) using L-arginine as a substrate. Three isoforms of NOS have been described: calcium-dependent endothelial (eNOS) and neuronal (nNOS) isoforms and inducible NOS. The expression and activity

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“…In addition, the dose-response curve was not linear when high concentrations of arginine were used in NOS assay. Thus, the working solution with the best specific activity was obtained in the presence of 120 nM of L-arginine with a fixed concentration of The dependence of the presence of co-substrate and cofactors in NOS activity have been reported in different tissue preparation, such as kidney, myenteric plexus, dorsal brain stem, neutrophils, dorsal periaquedutal gray, spinal cord and LLC-PK 1 cells (Lincoln, Messersmith, 1995;Mckee et al, 1994;Barjavel, Bhargava, 1995;Pontieri et al, 1998;Cerchiaro et al, 2001;Chiavegatto et al, 1998). Our results also demonstrated a dependence of the presence of co-factor when measuring NOS activity in platelet homogenate.…”

Section: Discussionmentioning

confidence: 99%