Cardiovascular Effects of Nitric Oxide and
            <i>N</i>
            -Methyl-
            <scp>d</scp>
            -Aspartate Receptors in the Nucleus Tractus Solitarii of Rats

Lo, Wan-Chen; H, Lin; Ger, Luo‐Ping; Tung, Che‐Se; Tseng, Ching‐Jiunn

doi:10.1161/01.hyp.30.6.1499

Cited by 55 publications

(51 citation statements)

References 26 publications

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“…14 We have recently demonstrated that NO can cause regulation of blood pressure in the central nervous system. 2,15,16 These data strongly suggest that the insulin-PI3K-Akt-NOS signaling pathway in the NTS is involved in central cardiovascular regulation.In the present study, we investigated the cardiovascular effects of insulin in the NTS of Wistar-Kyoto (WKY) rats of different ages. Our results showed that insulin and its downstream molecules, such as PI3K, Akt, and NOS, are involved in the regulation of central cardiovascular effects in the NTS of WKY rats.…”

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confidence: 78%

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confidence: 78%

“…The preparation of animals for intra-NTS microinjection and the methods used in localization of the NTS have been described previously. 15 A polyethylene cannula was inserted into the femoral vein for administration of drugs, and blood pressure was measured directly via a cannula placed into the femoral artery and connected to a pressure transducer (P23 ID) and a polygraph (AT5000). HR was monitored continuously with a tachograph preamplifier (13-4615-65; Gould).…”

Section: Animals and Hemodynamic Measurementsmentioning

confidence: 99%

“…14 Fifth, our previous data have suggested that NO is involved in central cardiovascular regulation, and the depressor effect of NO in the NTS might be through inhibition of renal sympathetic nerve activity. 15,16 Sixth, a NOS inhibitor can cause attenuation of baroreflex activation in the NTS (Figure 4). These results suggest that the cardiovascular function of insulin might be mediated through the NOS signaling pathway in the NTS.…”

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confidence: 99%

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In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate

Huang

et al. 2004

Circulation

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Background-Previously, we have shown that nitric oxide (NO) plays a significant role in central cardiovascular regulation and modulates the baroreflex in the nucleus tractus solitarii (NTS) of rats. NO production is mediated by activation of NO synthase (NOS). Insulin signaling was involved in controlling peripheral blood pressure via the activation of endothelial NOS. Here, we investigated whether the insulin signal transduction pathway is involved in controlling central cardiovascular effects. Methods and Results-Insulin was injected into NTS of urethane-anesthetized male Wistar-Kyoto (WKY) rats.Unilateral microinjection (60 nL) of insulin (100 IU/mL) into the NTS produced prominent depressor and bradycardic effects in 8-and 16-week-old WKY rats. In addition, pretreatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the NOS inhibitor L-NAME into the NTS caused attenuation of the cardiovascular response evoked by insulin in either 8-or 16-week-old WKY rats. Western blot analysis showed a significant increase (2.6Ϯ0.4-fold; PϽ0.05) in Akt phosphorylation after insulin injection, whereas LY294002 abolished the insulin-induced effects. In situ Akt phosphorylation was found in NTS by immunohistochemistry analysis after injection of insulin. This in situ Akt phosphorylation was abolished significantly after injection of LY294002. Conclusions-Take together, these results suggest that the insulin-PI3K-Akt-NOS signaling pathway may play a significant role in central cardiovascular regulation. Key Words: insulin Ⅲ enzymes Ⅲ nitric oxide synthase N itric oxide (NO) has been indicated to affect sympathetic nerve activity, and it modulates blood pressure and heart rate (HR) in the nucleus tractus solitarii (NTS). 1,2 However, the mechanisms for these actions have not been clarified. NO is produced by NO synthase (NOS). 3 Previously, adenovirusmediated gene delivery of endothelial NOS (eNOS) into NTS caused hypotension and bradycardia. 4 The results suggested that genes involved in the eNOS upstream signal transduction pathway might control central cardiovascular effects.Studies have shown that insulin receptors are present in the central nervous system, 5 which indicates the significant role of insulin in the central nervous system. Havrankova et al 6 have demonstrated that insulin has an effect on cardiovascular function. Other reports also showed the effects of insulin on arterial pressure and HR after peripheral injection and suggested a function of insulin in central cardiovascular control. 7,8 Recent evidence has demonstrated that the peripheral and central influence by insulin on cardiovascular regulation is due to an influence it exerts in the sympathetic nervous system. 7 Moreover, insulin receptors are shown to be immunochemically positive in the NTS. 8 These data suggested that insulin-mediated signaling in the NTS may play a significant role in the regulation of cardiovascular activity.It then becomes important to study insulin-mediated signaling in the NTS to understand how insulin regul...

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confidence: 78%

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confidence: 78%

Section: Animals and Hemodynamic Measurementsmentioning

confidence: 99%

mentioning

confidence: 99%

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In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate

Huang

et al. 2004

Circulation

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“…14 Furthermore, it has been reported that perfusion of adenosine through a microdialysis probe can increase the release of glutamate in the NTS. 11 17,19,20 CO is a second simple diatomic gas molecule that shares some physicochemical properties of NO. These studies suggest that CO may be a neurotransmitter in the nervous system.…”

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Interaction of Carbon Monoxide and Adenosine in the Nucleus Tractus Solitarii of Rats

Lin

Hsiao

et al. 2003

Hypertension

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Abstract-Carbon monoxide has been identified as an endogenous biological messenger in the brain. Heme oxygenase catalyzes the metabolism of heme to carbon monoxide and biliverdin. Previously, we have shown the involvement of carbon monoxide in central cardiovascular regulation, baroreflex modulation, and glutamatergic neurotransmission in the nucleus tractus solitarii of rats. We also showed that adenosine increased the release of glutamate in the nucleus tractus solitarii. In this study, we investigated the possible interactions of carbon monoxide and adenosine in the nucleus tractus solitarii. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure were monitored intra-arterially. Unilateral microinjection of increasing doses of hemin (0.01 to 3.3 nmol), a heme molecule cleaved by heme oxygenase to yield carbon monoxide, produced a significant decrease in blood pressure and heart rate in a dose-dependent manner. In addition, similar cardiovascular effects were observed after injection of adenosine (2.3 nmol). These cardiovascular effects of hemin were attenuated by prior administration of the adenosine receptor antagonist 1,3-dipropyl-8-sulfophenylxanthine. Similarly, pretreatment of the heme oxygenase inhibitor zinc protoporphyrin IX or zinc deuteroporphyrin 2,4-bis glycol also attenuated the depressor and bradycardic effects of adenosine.These results indicate that the interaction between carbon monoxide and adenosine may contribute to the activation of heme oxygenase in central cardiovascular regulation. Key Words: central nervous system Ⅲ blood pressure Ⅲ adenosine Ⅲ heart rate Ⅲ neuroregulators T he gaseous compound carbon monoxide (CO), a new neuromodulator agent, has been shown to play a role as a neurotransmitter. 1 In animals, the predominant source of CO generation is from heme degradation. Heme oxygenase (HO) is the rate-limiting enzyme responsible for the catabolism of heme and subsequent production of CO and biliverdin. Three isoforms of HO have been identified. HO-1, induced by heme and numerous oxidative stressors, is enriched in spleen and liver. HO-2 is present abundantly in the brain and testis as a constitutive enzyme. HO-3 has been identified in brain, heart, kidney, liver, testis, and spleen. 1 Studies have suggested that CO arising from heme through metabolism by HO stimulates soluble guanylate cyclase (sGC) activity and promotes an increase in cGMP in neural and cardiovascular tissues. [2][3][4] These results implicate the HO/CO system as a potential regulator of various neural and cardiovascular functions.HO is widely expressed in the brain and is responsible for the CO-generating ability of the brain, including brain stem. 2,5 In the central nervous system (CNS), the nucleus of the solitary tract (NTS) is the site where afferent fibers arising from arterial baroreceptor, chemoreceptors, cardiopulmonary receptors, and other visceral receptors form the first central synapses 6 and thus play an important role in the integration of autonomic control of the cardiovascul...

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Cardiovascular responses and nitric oxide production in cerebral ischemic rats

Shin

Lee

et al. 2002

Arch Pharm Res

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We investigated that the role of nitric oxide (NO) on ischemic rats in brain and heart. Ischemia was induced by both common carotid arteries (CCA) occlusion for 24h following reperfusion. Then tissue samples were removed and measured NOx. In brain, NOx was increased by about 40% vs. normal and it was significantly inhibited by aminoguanidine, selective iNOS inhibitor. This result showed that NOx concentration was increased by iNOS. We investigated the role of Ca2+ during ischemia. Nimodipine, L-type calcium channel blocker, didn't inhibit the increases of NOx concentration during ischemia. It suggested that increased NOx was due to calcium-independent NOS. MK-801, which N-methyl-D-aspartate (NMDA) receptor antagonist, didn't significantly prevent the increases of NOx. In heart, ischemia caused NOx decrease and it is inconsistent with NOx increase in brain. Aminoguanidine and nimodipine didnt affect on NOx decrease. But MK-801 more lowered NOx concentration than those of ischemia control group. It seemed that Ca2+ influx in heart partially occurred via NMDA receptor and inhibited by NMDA receptor antagonist. The mean arterial pressure (MAP) in ischemic rats after 24h of CCA occlusion was decreased when compared to normal value, whereas the heart rates (HR) was not different between two groups. Aminoguanidine or MK801 had no effect on MAP or HR, but nimodipine reduced MAP. There was no difference the effects of aminoguanidine, nimodipine, or MK-801, on MAP and HR between normal rats and ischemic rats. In summary, ischemic model caused an increase of NOx concentration, suggesting that this may be produced via iNOS, which is calcium independent in brain. However in heart, ischemia decreased NOx concentration and NMDA receptor was partially involved. The basal MAP was decreased in ischemic rats but HR was not different from normal control, suggesting that increased NOx in brain of ischemic rat may result in the hypotension.

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Cardiovascular Effects of Nitric Oxide and N -Methyl- d -Aspartate Receptors in the Nucleus Tractus Solitarii of Rats

Cited by 55 publications

References 26 publications

In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate

In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate

Interaction of Carbon Monoxide and Adenosine in the Nucleus Tractus Solitarii of Rats

Cardiovascular responses and nitric oxide production in cerebral ischemic rats

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