Brain neuronal nitric oxide synthase neuron-mediated sympathoinhibition is enhanced in hypertensive Dahl rats

Tandai-Hiruma, Megumi; Horiuchi, Jouji; Sakamoto, Hiroshi; Kemuriyama, Takehito; Hirakawa, Haruhisa; Nishida, Yasuhiro

doi:10.1097/01.hjh.0000163152.27954.7a

Cited by 18 publications

(35 citation statements)

References 39 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neurally derived NO (nNO) modulates blood pressure primarily through its interaction with the autonomic nervous system, mainly through inhibition of central sympathetic outflow. 1,2 There is controversy about the relative contribution of eNO and nNO in the regulation of blood pressure. Mice made deficient of NOS3 have a significant increase in baseline blood pressure, 3 whereas mice lacking NOS1 do not.…”

mentioning

confidence: 99%

Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

Gamboa¹,

Shibao²,

Diedrich³

et al. 2007

Hypertension

View full text Add to dashboard Cite

Abstract-Impaired endothelial-derived NO (eNO) is invoked in the development of many pathological conditions. Systemic inhibition of NO synthesis, used to assess the importance of NO to blood pressure (BP) regulation, increases BP by Ϸ15 mm Hg. This approach underestimates the importance of eNO, because BP is restrained by baroreflex mechanisms and does not account for a role of neurally derived NO. To overcome these limitations, we induced complete autonomic blockade with trimethaphan in 17 normotensive healthy control subjects to eliminate baroreflex mechanisms and contribution of neurally derived NO. Under these conditions, the increase in BP reflects mostly blockade of tonic eNO. N G -Monomethyl-L-arginine (250 g/kg per minute IV) increased mean BP by 6Ϯ3.7 mm Hg (from 77 to 82 mm Hg) in intact subjects and by 21Ϯ8.4 mm Hg (from 75 to 96 mm Hg) during autonomic blockade. We did not find a significant contribution of neurally derived NO to BP regulation after accounting for baroreflex buffering. To further validate this approach, we compared the effect of NOS inhibition during autonomic blockade in 10 normotensive individuals with that of 6 normotensive smokers known to have endothelial dysfunction but who were otherwise normal. As expected, normotensive smokers showed a significantly lower increase in systolic BP during selective eNO blockade (11Ϯ4.

show abstract

mentioning

confidence: 99%

Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

Gamboa¹,

Shibao²,

Diedrich³

et al. 2007

Hypertension

View full text Add to dashboard Cite

show abstract

“…When 7-nitroindazole, an nNOS inhibitor, was administered systemically to rats in an unanesthetized, unrestrained state, peripheral sympathetic nerve activity increased significantly [38]. Moreover, when S-methyl-L-thiocitrulline (SMTC), an inhibitor with high specificity, was administered intraventricularly to rats in the same unanesthetized, unrestrained state, a similar rise was seen in resting peripheral sympathetic nerve activity as well as in blood pressure [39] Dahl salt-sensitive rats fed an 8% NaCl diet (high-salt diet); DS0.4%: Dahl salt-sensitive rats fed a 0.4% NaCl diet (regular diet); DR8%: Dahl saltresistant rats fed an 8% NaCl diet; DR0.4%: Dahl salt-resistant rats fed a 0.4% NaCl diet; SAP: systolic arterial pressure measured with the tail cuff method in conscious rats; Age: rat age. *: p < 0.005 vs. DS0.4%; †: p < 0.05 vs. the initial (8-week) value for DS8%.…”

Section: Central Inhibitory System Of Sympathetic Nervesmentioning

confidence: 80%

“…RSNA signals after these peak responses were produced by animal movements because of hypotension. Both resting RSNA and the peak response obtained by the release of baroreflex-mediated negative feedback inhibition (baroreceptor-unloaded RSNA, which indicates central sympathetic activity generated before baroreflex inhibition) were markedly increased after SMTC infusion [39]. pressure agonistic sympathetic nerve centers; 2) when inhibition is blocked, the activity of the rostral ventrolateral medulla (generator neurons of sympathetic nerve centers [39,42]) increases; and 3) the central inhibitory system is upregulated in salt-sensitive hypertensive Dahl rats.…”

Section: Map (Mmhg)mentioning

confidence: 99%

“…Attempts were made to measure renal sympathetic nerve activity at rest in an unanesthetized, unrestrained free movement state [38,39]. In actuality, this is not a simple thing to do.…”

Section: Peripheral Sympathetic Nerve Activitymentioning

confidence: 99%

“…Brainstem-tissue nNOS activity and nNOS protein amount were compared between 4 rats groups (salt-sensitive normotensive Dahl rats, salt-sensitive hypertensive Dahl rats, salt-resistant Dahl rats fed regular diet, salt-resistant Dahl rats fed high-salt diet) [39]. Both of brainstem nNOS activity and nNOS protein amount were significantly higher in the DS8% hypertensive group than in the other 3 normotensive ratgroups, and no significant difference was found in both of activity and protein amount between the 3 normotensive rat-groups (salt-sensitive normotensive Dahl rats, salt-resistant Dahl rats fed regular diet, saltresistant Dahl rats fed high-salt diet) [39].…”

Section: Central Nnos Neuronsmentioning

confidence: 99%

See 2 more Smart Citations

Sympathetic Activity in Dahl Salt-Sensitive Hypertension - Why is a Nitric Oxide-Induced Inhibitory System Up-Regulated in the Sympathetic Center?

Nishida¹

2013

J Nephrol Ther

Self Cite

View full text Add to dashboard Cite

In essential hypertension, peripheral sympathetic nerve activity is generally thought to be increased regardless of salt sensitivity or insensitivity. Recent reports suggest that the cause may be abnormal central nervous system enhancement. However, other several reports have shown that a central sympathetic inhibitory system, the neuronal nitric oxide synthase system, may be strongly enhanced in salt-sensitive hypertensive Dahl rats, an animal model of salt-sensitive hypertension. These two facts lead to questions what happens finally in peripheral sympathetic activity and what is the relationship between sympathetic nerves and hypertension. In this review, we will show evidences for enhancement of central sympathetic inhibitory system, putative cause for up-regulation of central neuronal nitric oxide synthase system, and a role of its function, then lastly we consider the relationship between hypertension and sympathetic nerves in a rat model, with a focus on salt-sensitive hypertension.

show abstract

Endogenous angiotensin II has fewer effects but neuronal nitric oxide synthase has excitatory effects on renal sympathetic nerve activity in salt-sensitive hypertension-induced heart failure

et al. 2009

Self Cite

View full text Add to dashboard Cite

The effects of endogenous angiotensin II (Ang II) and neuronal nitric oxide synthase (nNOS) on tonic sympathetic activity were studied in salt-sensitive hypertension-induced heart failure. Dahl salt-sensitive rats were fed 8% NaCl diet for 9 weeks to induce chronic heart failure (CHF-DSS). The effects of intravenous administration of a selective nNOS inhibitor, S-methyl-L: -thiocitrulline (SMTC), and an Ang II type 1-receptor blocker, losartan, on renal sympathetic nerve activity (RSNA) were examined in chronically instrumented conscious rats. Baroreceptor (baro)-unloaded RSNA was obtained by decreasing arterial pressure with caval occlusion to determine tonic RSNA. SMTC significantly decreased baro-unloaded RSNA, and subsequent losartan recovered baro-unloaded RSNA to the control level in CHF-DSS rats. To compare the effects of the inhibitors between low- and high-activity states of the renin-angiotensin system (RAS), Sprague-Dawley rats were fed low (0.04%)- or high (8%)-salt diets. A significant difference was found in the effects of SMTC and/or losartan on RSNA between the high- and low-RAS states, which suggested that there is a difference in the effect of endogenous Ang II on RSNA between salt-induced and other-type heart failure. To examine the effects of heart failure on brain-tissue nNOS activity, we measured the activities of the diencephalon in heart-failure rats. Heart failure significantly suppressed diencephalon nNOS activity, which was significantly different from the results in salt-sensitive hypertension without heart failure. These results suggest that endogenous Ang II has fewer effects, but nNOS has excitatory effects on tonic RSNA in salt-sensitive hypertension-induced heart failure.

show abstract

Brain neuronal nitric oxide synthase neuron-mediated sympathoinhibition is enhanced in hypertensive Dahl rats

Abstract: These findings suggest that central nNOS-mediated sympathoinhibition may be enhanced in salt-sensitive hypertensive Dahl rats. The upregulated nNOS-mediated inhibition may occur in the central sympathetic control system generated before baroreflex-mediated inhibition.

Cited by 18 publications

References 39 publications

Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

Sympathetic Activity in Dahl Salt-Sensitive Hypertension - Why is a Nitric Oxide-Induced Inhibitory System Up-Regulated in the Sympathetic Center?

Endogenous angiotensin II has fewer effects but neuronal nitric oxide synthase has excitatory effects on renal sympathetic nerve activity in salt-sensitive hypertension-induced heart failure

Contact Info

Product

Resources

About