Reflex arc of the teeth clenching-induced pressor response in rats.

Although "teeth clenching" induces pressor response, the reflex tracts of the response are unknown. In this study, dantrolene administration inhibited teeth clenching generated by electrical stimulation of the masseter muscles and completely abolished the pressor response. In addition, trigeminal ganglion block or hexamethonium administration completely abolished the pressor response. Local anesthesia of molar regions significantly reduced the pressor response to 27 ± 10%. Gadolinium (mechanoreceptor blocker of group III muscle afferents) entrapment in masticatory muscles also significantly reduced the pressor response to 62 ± 7%. Although atropine methyl nitrate administration did not change the pressor response, a significant dose-dependent augmentation of heart rate was observed. These results indicate that both periodontal membrane and mechanoreceptors in masticatory muscles are the receptors for the pressor response, and that the afferent and efferent pathways of the pressor response pass through the trigeminal afferent nerves and sympathetic nerves, respectively.

Mismatch between peripheral and central demands in salt-sensitive hypertensive Dahl rats.

Sympathetic nerve activity in essential hypertension, which accounts for 90% of all hypertension cases, is in general thought to be elevated regardless of whether there is salt sensitivity or insensitivity. The cause is thought to be an abnormality in the sympathetic center. On the other hand, neuronal nitric oxide synthase-expressing neurons that function to inhibit the sympathetic center are clearly activated in the salt-sensitive hypertensive Dahl rat model. How is this related to sympathetic hyperactivity and hypertension? Also, how is hypertension associated with peripheral vessel contractility and renal function? Human life is supported by the body's various essential functions. The circulatory system links all these functions into one system that cannot be separated. Blood pressure is the driving force of this circulatory system, and both the central and peripheral demands determine the output. We examined the 'mismatch' between these two sides and its association with hypertension.

High blood pressure enhances brain stem neuronal nitric oxide synthase activity in Dahl salt-sensitive rats.

The aims of the present study were to determine the mechanism underlying enhanced neuronal nitric oxide synthase (nNOS) activity in the brain of hypertensive Dahl salt-sensitive (DSS) rats and the consequences of enhanced nNOS activity. Male DSS rats were fed either a regular (0.4% NaCl) or high-salt (8% NaCl) diet, with or without 0.25% nifedipine, for 4 weeks. The effects of nifedipine, which lowers blood pressure peripherally, on central nNOS were determined by measuring nNOS activity, as well as the number of nNOS-positive neurons in the brain stem and diencephalon. The effects of chronic (12 days) infusion of 7 µg (0.5 µL/h, i.c.v.) S-methyl-L-thiocitrulline (SMTC; a stereoselective competitive nNOS inhibitor) on mean arterial pressure were assessed in conscious DSS rats using a radiotelemetry system. In addition, the number of central nNOS-positive neurons was compared between DSS and salt-insensitive Sprague-Dawley rats. Normalization of blood pressure by nifedipine attenuated the increase in nNOS activity in the brain stem of DSS rats. Chronic i.c.v. infusion of SMTC further enhanced hypertension in DSS rats. Feeding of a high-salt diet increased nNOS-positive neurons in the lateral parabrachial nucleus, rostral ventrolateral medulla and nucleus tractus solitarius of DSS compared with Sprague-Dawley rats, whereas nNOS-positive neurons in the paraventricular nucleus remained downregulated in DSS rats. The results of the present study suggest that hypertension, rather than a high-salt diet, increases central nNOS activity in hypertensive DSS rats to buffer high blood pressure. However, this compensatory response may be insufficient to relieve salt-induced hypertension.

Paired stimulation between CA3 and CA1 alters excitability of CA3 in the rat hippocampus.

It is generally accepted that the extent of plasticity is localized to the region around synapses and post-synaptic intracellular signaling cascades. We investigated the presence of long-range retrograde plasticity associated with excitability at pre-synaptic neurons (CA3) and regulated by the firing of post-synaptic neurons (CA1). We used acute hippocampus slices from transgenic rats expressing channelrhodopsin-2 (ChR2) in both CA1 and CA3 neurons. We employed a parallel photostimulation technique, which enabled robust and independent evocation of action potentials in either CA3 or CA1 neurons. Optically evoked CA3 firings were paired either with CA1 simultaneous firings or with CA1 suppression after the prolonged stimulation. Pre-synaptic excitability was monitored by measuring the optically-evoked firing rate (Opt-FR). We found that the Opt-FR of CA3 neurons was long-term up-regulated as a result of synchronous pre- and post-synaptic pairing stimulation, but down-regulated by the pre-synaptic stimulation during post-synaptic suppression. Both pairing-dependent up-regulation and down-regulation were retarded by NMDA receptor blocking or colchicine preincubation. This finding suggest that CA3 excitability is regulated by CA1 neuron activity at the time of CA3 firing.

Long-term blood pressure control: is there a set-point in the brain?

Mean arterial pressure fluctuates depending on physical or psychological activity, but should be stable at rest at around 100 mmHg throughout an entire life in human. The causes of hypertension and the blood pressure regulation mechanisms have been discussed for a long time, and many aspects have recently become more clear. Circulatory shock or short-term hypotension can be treated based on what is now known, but chronic hypertension is still difficult to treat thoroughly. The exact mechanisms for long-term blood pressure regulation have yet not been elucidated. Neuro­humoral interaction has been suggested as one of the mechanisms. Then, from the 1990s, paracrine hormones like nitric oxide or endothelins have been extensively researched in order to develop endothelial local control mechanisms for blood pressure, which have some relationships to long-term control. Although these new ideas and mechanisms are newly developed, no clear explanation for long-term control has yet been discussed, except for renal abnormality. Recently, a central set-point theory has begun to be discussed. This review will discuss the mechanisms for long-term blood pressure control, based on putative biological missions of circulatory function for life support.

A power-law distribution of inter-spike intervals in renal sympathetic nerve activity in salt-sensitive hypertension-induced chronic heart failure.

To assess sympathetic variability in chronic heart failure (CHF), we evaluated a distribution of inter-spike intervals (ISIs) in renal sympathetic nerve activity (RSNA) in salt-sensitive hypertension-induced CHF (DSSH-CHF) rats. Dahl salt-sensitive rats were fed an 8% NaCl diet for 9 weeks to induce salt-sensitive hypertension-induced CHF. ISIs in RSNA were obtained from chronically instrumented conscious rats, and counts (frequency) and ranks of ISIs in RSNA were plotted with a histogram. We found that ISIs in RSNA followed a power-law distribution in rats, and the power-law distribution of ISIs for RSNA in DSSH-CHF rats was significantly different from that in normal rats. These results indicated that sympathetic variability may be significantly different between salt-sensitive hypertension-induced CHF and healthy individuals, which suggests that sympathetic variability may be used to predict abnormality of the sympathetic regulatory system.

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.

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.

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

OBJECTIVE: To elucidate the role of central neurons containing neuronal nitric oxide synthase (nNOS neurons) in the sympathetic nervous system in hypertensive Dahl salt-sensitive (DS) rats. DESIGN AND METHODS: Dahl rats were fed either a regular-salt (0.4% NaCl) or high-salt (8% NaCl) diet for 4 weeks. The effect of intracerebroventricular administration of S-methyl-L-thiocitrulline, a selective nNOS inhibitor, on renal sympathetic nerve activity was examined in chronically instrumented conscious DS rats. The activity and protein amount of brain nNOS was evaluated by enzyme assay and western blot analysis. The distribution and number of nNOS neurons in the brainstem were examined immunohistochemically in hypertensive and normotensive DS rats. RESULTS: S-methyl-L-thiocitrulline induced a larger increase in tonic renal sympathetic nerve activity generated before baroreflex-mediated inhibition in hypertensive DS rats than normotensive DS rats. Hypertensive DS rats showed increased nNOS activity in the brainstem, but not in the diencephalon or cerebellum. High nNOS activity was confirmed by an increase in the amount of nNOS protein. nNOS Neurons were localized in several nuclei throughout the brainstem; the dorsolateral periaqueductal gray, pedunculopontine tegmental nucleus, dorsal raphe nucleus, laterodorsal tegmental nucleus, lateral parabrachial nucleus, rostral ventrolateral medulla, nucleus tractus solitarius and raphe magnus. The number of nNOS neurons in these nuclei, except for the two raphes, was significantly greater in hypertensive than in normotensive DS rats. CONCLUSIONS: 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.