gamma-Aminobutyric acid in the lateral septal area is involved in mediation of the inhibition of hypothalamic angiotensin II-sensitive neurons induced by blood pressure increases in rats.

Previously, we have demonstrated that intravenous phenylephrine-induced increases in blood pressure inhibit angiotensin II-sensitive neurons via gamma-aminobutyric acid (GABA) inputs in the anterior hypothalamic area (AHA). The lateral septal area (LSV) is also demonstrated to be involved in mediation of the baroreceptor reflex. To investigate central mechanisms involved in mediating the baroreceptor reflex, we examined whether GABA in the LSV is involved in mediation of the phenylephrine-induced inhibition of AHA angiotensin II-sensitive neurons.

Intracerebroventricular injection of losartan inhibits angiotensin II-sensitive neurons via GABA inputs in the anterior hypothalamic area of rats.

Previously, we have demonstrated that pressure-ejected application of angiotensin II and losartan, an angiotensin AT1 receptor antagonist, onto some neurons in the anterior hypothalamic area (AHA) of the rat increases and decreases, respectively, the basal firing rate of the neurons. To investigate possible participation of these AHA neurons in the brain angiotensin system, we examined whether intracerebroventricular injection of the angiotensin AT1 receptor antagonist losartan inhibits the neuronal activity of angiotensin II-sensitive neurons via GABA inputs in the AHA of rats. Intracerebroventricular injection of losartan decreased the firing rate of AHA angiotensin II-sensitive neurons.

Centrally injected angiotensin II trans-synaptically activates angiotensin II-sensitive neurons in the anterior hypothalamic area of rats.

Previously, we have demonstrated that pressure-ejected application of angiotensin II onto some neurons in the anterior hypothalamic area (AHA) of rats increases their firing rate. In contrast, pressure application of the angiotensin AT1 receptor antagonist losartan onto AHA neurons blocked the basal firing of the neurons. To investigate possible participation of these AHA neurons in the brain angiotensin system, we examined whether intracerebroventricular injection of angiotensin II results in an activation of angiotensin II-sensitive neurons in the AHA of rats.

[Mechanisms of hypertension in the central nervous system].

This article reviews studies by the author on central mechanisms of hypertension. Spontaneously hypertensive rats (SHR) have been developed as a rat model of genetic hypertension, and central acetylcholine has been implicated in hypertension in SHR. The rostral ventrolateral medulla (RVL), a major source of efferent sympathetic activity, has cholinergic pressor systems.

Evidence suggesting that angiotensins released not via synaptic inputs are involved in the basal activity of anterior hypothalamic neurons in rats.

Previously, we have demonstrated that angiotensin II-sensitive neurons exist in the anterior hypothalamic area (AHA) and that these neurons are tonically activated by endogenous angiotensins in rats. Chemical stimulation of the lateral septal area (LSV) and medial amygdaloid nucleus (MeA), and intracerebroventricular injection of hypertonic saline, activated AHA angiotensin II-sensitive neurons. To investigate mechanisms of the basal activity of AHA angiotensin II-sensitive neurons, we examined the effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7), a calmodulin inhibitor, applied onto AHA neurons on the basal activity and the stimulus-evoked activation of these neurons.

Sensitivity of pressor responses to central hypertonic saline is greatly enhanced even in pre-hypertensive spontaneously hypertensive rats.

It has been suggested that intracerebroventricular injection of hypertonic saline mimics the effects of a high salt diet in spontaneously hypertensive rats (SHR), a genetic model of hypertension. Intracerebroventricular injection of hypertonic saline produces an increase in blood pressure and the pressor response to hypertonic saline is enhanced in adult hypertensive SHR. In this study, we examined whether the intracerebroventricular hypertonic saline-induced pressor response is enhanced even in pre-hypertensive SHR.

Angiotensin II sensitivity of anterior hypothalamic area neurons is enhanced in both spontaneously hypertensive rats and Dahl salt-sensitive rats.

We have previously demonstrated that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins. Furthermore, we have demonstrated that intracerebroventricular injection of hypertonic saline increases the firing rate of AHA angiotensin II-sensitive neurons via angiotensins and that the central sodium-induced activation of AHA neurons is enhanced in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (Dahl S) rats. In this study, we examined whether sensitivities of AHA angiotensin II-sensitive neurons to angiotensin II are enhanced in SHR and Dahl S rats as compared with their respective controls.

Activities of hypothalamic angiotensin II-sensitive neurons are greately enhanced even in prehypertensive spontaneously hypertensive rats.

We have previously demonstrated that some neurons in the anterior hypothalamic area (AHA) of rats are tonically activated by endogenous angiotensins and that reactivities of these neurons to angiotensin II are enhanced in 15- to 16-week-old spontaneously hypertensive rats (SHR). To investigate whether the enhanced reactivity of SHR AHA neurons to angiotensin II is secondary to raised blood pressure, we examined whether the enhanced reactivity to angiotensin II also occurs in prehypertensive SHR. We also examined whether reactivities of AHA angiotensin II-sensitive neurons to intracerebroventricular hypertonic saline are enhanced in prehypertensive SHR, since intracerebroventricular injection of hypertonic saline increases the firing rate of AHA neurons via release of angiotensins at AHA neuron levels.

Enhanced central hypertonic saline-induced activation of angiotensin II-sensitive neurons in the anterior hypothalamic area of spontaneously hypertensive and Dahl S rats.

High dietary salt intake activates the brain renin-angiotensin system in spontaneously hypertensive rats (SHR) and Dahl S rats, resulting in sympathetic hyperactivity and hypertension. Increases of sodium concentration in cerebrospinal fluid (CSF) and/or enhanced responses to CSF sodium are considered to be involved in the high dietary salt-induced activation of central nervous system pathways in those rats. Previously we have demonstrated that intracerebroventricular injection of hypertonic saline increases the neural activity of angiotensin II-sensitive neurons trans-synaptically via endogenous angiotensins in the anterior hypothalamic area (AHA) of rats.

Posterior hypothalamus cholinergic stimulation-induced activation of anterior hypothalamic area neurons is enhanced in spontaneously hypertensive rats.

We have previously demonstrated that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA neurons are enhanced in spontaneously hypertensive rats (SHR). In addition, we have demonstrated that cholinergic mechanisms in the posterior hypothalamic nucleus (PHN) are involved in the activation of AHA angiotensin-II-sensitive neurons. It has been suggested that cholinergic function in the posterior hypothalamus is enhanced in SHR and that this hyperactivity plays a role in hypertension in SHR.

Cholinergic stimulation in the posterior hypothalamic nucleus activates angiotensin II-sensitive neurons in the anterior hypothalamic area of rats.

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats (SHR). Acetylcholine in the posterior hypothalamic nucleus (PHN) has been implicated in hypertension in SHR. It is suggested that there exist neuronal projections from the PHN to the AHA in rats.

Cholinergic systems in the posterior hypothalamic nucleus are involved in blood pressure decrease-induced excitation of anterior hypothalamic area neurons in rats.

Previously, we have demonstrated that decreases in blood pressure induced by intravenous nitroprusside increase the firing rate of angiotensin II-sensitive neurons in the anterior hypothalamic area (AHA) of rats and that this increase of neural firing rate is blocked by the pressure application of losartan onto the same neurons. It has been suggested that acetylcholine in the posterior hypothalamic nucleus (PHN) serves as a neurotransmitter in a pathway which can modulate baroreceptor reflexes. In the present study, we examined whether acetylcholine in the PHN is involved in the nitroprusside-induced increase of the firing of angiotensin II-sensitive neurons in the AHA of rats.

Cholinergic stimulation in the lateral septal area activates anterior hypothalamic area neurons via excitatory amino acid receptors in rats.

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats. It is suggested that there exist neuronal projections from the lateral septal area (LSV) to the AHA in rats. In this study, we examined whether neurons in the LSV are involved in activation of AHA angiotensin II-sensitive neurons.

Anterior hypothalamic neurons respond to blood pressure changes via gamma-aminobutyric acid and angiotensins in rats.

It has been suggested that neurons in the hypothalamus respond to baroreflex activation and deactivation. In this study, we examined whether angiotensin II-sensitive neurons in the anterior hypothalamic area (AHA) respond to baroreflex activation and deactivation, and which neurotransmitters are involved in mediating the baroreflex responses. Male Wistar rats were anesthetized and artificially ventilated.

Central injection of hypertonic saline activates angiotensin II-sensitive neurons in the anterior hypothalamic area of rats.

We have previously reported that microinjection of angiotensin II into the anterior hypothalamic area (AHA) produces pressor responses and that angiotensin II-sensitive neurons in the AHA are tonically activated by endogenous angiotensins in rats. Central injection of hypertonic saline causes pressor responses via release of angiotensins in brain. In this study, we examined whether angiotensin II-sensitive neurons in the AHA are responsive to intracerebroventricular injection of hypertonic saline and whether endogenous angiotensins in the AHA are involved in the central hypertonic saline-induced pressor response.

Role of protein kinase C beta in phorbol ester-induced c-fos gene expression in neurons of normotensive and spontaneously hypertensive rat brains.

We have previously demonstrated that pressure application of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) onto some neurons in the anterior hypothalamic area of rats increases neural activity in vivo and that this PKC activation-induced increase of neural activity is enhanced in spontaneously hypertensive rats (SHR), an animal model for genetic hypertension. Activation of PKC increases expression of the c-fos gene, an important transcription factor and proto-oncogene thought to be a marker of neural activity. To evaluate PKC isoforms responsible for neural activation, we examined which isoforms of PKC are involved in the PKC activation-induced c-fos gene expression in neuronal cultures of Wistar rat and spontaneously hypertensive rat (SHR) brains.

Protein kinase C activation-induced increases of neural activity are enhanced in the hypothalamus of spontaneously hypertensive rats.

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these angiotensin II-sensitive neurons in the AHA are enhanced in spontaneously hypertensive rats (SHR). In addition, neural activations induced by both angiotensin II and glutamate were enhanced in the AHA of SHR. In this study, we examined whether intracellular neural activation mechanisms via protein kinase C (PKC) and a potassium channel are altered in angiotensin II-sensitive neurons in the AHA of SHR.

The medial amygdaloid area is involved in activation of angiotensin II-sensitive neurons in the anterior hypothalamic area.

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that the activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats. It is suggested that there exist neural projections from the medial amygdala to the AHA in rats. In this study, we examined whether neurons in the medial amygdaloid area (MeA) are involved in the activation of AHA angiotensin II-sensitive neurons.

Enhanced activity of angiotensin II-sensitive neurons in the anterior hypothalamic area of spontaneously hypertensive rats.

We have previously reported that an angiotensin system in the anterior hypothalamic area (AHA) is enhanced in spontaneously hypertensive rats (SHRs) and that this enhancement is involved in hypertension in this strain. In addition, we have reported that some neurons in the AHA are tonically activated by endogenous angiotensins in rats. In this study, we examined whether activities of neurons receiving tonic angiotensinergic inputs in the AHA are enhanced in SHR as compared with those of Wistar Kyoto rats (WKY).

Contribution of the medial amygdaloid nucleus to the development of hypertension in spontaneously hypertensive rats.

We previously demonstrated involvement of the medial amygdaloid nucleus in restraint stress-induced pressor responses in rats. In this study, neuronal perikarya in the medial amygdaloid nucleus of 4-week-old spontaneously hypertensive rats (SHR) were selectively destroyed with ibotenic acid. Bilateral lesions of the medial amygdaloid nucleus attenuated the development of hypertension in SHR.

Tonic angiotensinergic inputs to neurons in the anterior hypothalamic area of rats.

We have previously reported that microinjection of angiotensin II into the anterior hypothalamic area (AHA) produces a pressor response in rats and that the angiotensin AT1 receptor antagonist, losartan, similarly injected causes a depressor response in hypertensive rats. In this study, we examined whether endogenous angiotensins are involved in activation of neurons in the AHA. Male Wistar rats were anesthetized and artificially ventilated.

Basal transcriptional regulation of rat AT1 angiotensin II receptor gene expression.

1. Angiotensin II AT1A receptors are thought to play an important role in the development of hypertension. The transcriptional factor Sp1 is a ubiquitous transcriptional factor associated with GC-rich promoters and involved in basal promoter activity.

Involvement of the medial amygdaloid nucleus in restraint stress-induced pressor responses in rats.

Restraint stress increased the number of neurons with Fos immunoreactivity in the medial amygdaloid nucleus in rats and caused an increase in blood pressure. The stress-induced pressor response was inhibited by muscimol (80 pmol), a neuroinhibitory compound, injected bilaterally into the medial amygdaloid area, whereas muscimol (8 pmol) similarly injected had only a tendency of inhibition of the pressor response. These data suggest that the medial amygdaloid nucleus is involved in mediation of the restraint stress-induced pressor response.

Sp1 decoy oligodeoxynucleotide decreases angiotensin receptor expression and blood pressure in spontaneously hypertensive rats.

The transcriptional factor Sp1 is associated with GC-rich promoters and involved in basal promoter activity. A GC-box-related sequence is located within the -58 to -34 base pair region of the angiotensin type 1 receptor gene promoter. We examined whether Sp1 in the hypothalamus was increased in spontaneously hypertensive rats (SHR) and whether inhibition of Sp1 binding sites suppressed angiotensin type 1 receptor expression and thus decreased blood pressure in SHR.

Projections from the caudal part to the rostral part of the lateral septal area mediate blood pressure increase.

We previously demonstrated that restraint stress-induced pressor responses were inhibited by bilateral microinjection of muscimol into the rostral part of the ventral zone of the lateral septal area (LSV). The caudal part of the lateral septal area is also reported to be involved in blood pressure regulation. In this study, we examined whether the LSV receives projections from the caudal part of the dorsal zone of the lateral septal area (LSD) in rats.