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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. Microinjection of GABA into the LSV inhibited angiotensin II-sensitive neurons in the AHA of rats. The LSV GABA-induced inhibition of AHA neurons was abolished by pressure application of bicuculline onto the same AHA neurons. Intravenous injection of phenylephrine also inhibited AHA angiotensin II-sensitive neurons and the phenylephrine-induced inhibition of AHA neurons was abolished by microinjection of the GABAA receptor antagonist bicuculline into the LSV. In contrast, the LSV microinjection of bicuculline did not affect the inhibition of firing of AHA neurons induced by GABA pressure-applied in the AHA. These findings suggest that intravenous phenylephrine inhibits AHA angiotensin II-sensitive neurons via release of GABA in the LSV.

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. However, the intracerebroventricular injection of losartan did not affect the increase in firing rate of AHA angiotensin II-sensitive neurons induced by pressure application of angiotensin II onto the same neurons, although losartan similarly injected abolished the increase in firing rate of AHA angiotensin II-sensitive neurons induced by intracerebroventricular injection of angiotensin II. The losartan-induced decrease of unit firing in AHA neurons was abolished by pressure application of the GABAA receptor antagonist bicuculline onto the same neurons. Bicuculline itself did not affect the basal firing rate of AHA neurons. These findings suggest that intracerebroventricular injection of losartan inhibits AHA angiotensin II-sensitive neurons via GABA inputs to the neurons.

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. Intracerebroventricular injection of angiotensin II increased the firing rate of AHA angiotensin II-sensitive neurons. The angiotensin II-induced increase of unit firing in AHA neurons was abolished by pressure application of losartan onto the same neurons. In addition, the angiotensin II-induced increase of firing in AHA neurons was abolished by pressure application of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7), a calmodulin inhibitor, onto the same neurons. Pressure application of W7 onto AHA neurons affected neither the basal firing rate nor the increase in unit firing induced by pressure application of angiotensin II onto the same neurons. Intracerebroventricular injection of the cholinergic agonist carbachol did not affect the firing rate of angiotensin II-sensitive neurons in the AHA. These findings suggest that intracerebroventricular injection of angiotensin II activates AHA angiotensin II-sensitive neurons via angiotensinergic inputs to the neurons.

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. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjections of carbachol into the LSV and corticotropin-releasing factor into the MeA, and intracerebroventricular injection of hypertonic saline, activated AHA angiotensin II-sensitive neurons. These three kinds of injection-induced activations of AHA neurons were abolished by pressure application of W7 onto the same neurons, while the calmodulin inhibitor did not affect the increase in firing of AHA neurons induced by pressure application of angiotensin II onto the same neurons. The pressure application of W7 did not affect the basal activity of AHA angiotensin II-sensitive neurons, whereas the angiotensin AT1 receptor antagonist losartan similarly applied inhibited it. These findings suggest that the basal activity of AHA angiotensin II-sensitive neurons is mediated by angiotensins released not via synaptic inputs.

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. Male 15- to 16-week-old SHR and age-matched Wistar Kyoto rats (WKY), and male 15- to 16-week-old Dahl S rats and Dahl R rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. In SHR, pressure application of angiotensin II (3 x 10(-9) to 3 x 10(-8) M) onto AHA angiotensin II-sensitive neurons increased their firing rate in a concentration-dependent manner. In WKY, only the highest concentration of angiotensin II increased the firing rate, while the lower concentrations of angiotensin II did not affect it. In Dahl S rats, pressure application of angiotensin II (10(-8) and 3 x 10(-8) M) onto AHA neurons increased their firing rate, while angiotensin II (3 x 10(-9) M) did not affect it. In Dahl R rats, the highest concentration of angiotensin II increased the firing rate, while the lower concentrations of angiotensin II did not affect it. These findings indicate that the sensitivity of AHA neurons to angiotenisn II is enhanced in SHR and Dahl S rats as compared with their respective controls.

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. Male 4-week-old SHR and age-matched Wistar Kyoto rats (WKY) were used in this study. There was no difference in systolic blood pressure between both rats. They were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Pressure application of angiotensin II onto some AHA neurons increased their firing rate. The basal firing rate of angiotensin II-sensitive neurons was increased in SHR as compared with WKY. The increase of unit firing by angiotenisn II was enhanced in SHR as compared with WKY. Intracerebroventricular injection of hypertonic saline increased the firing rate of AHA angiotensin II-sensitive neurons. The average threshold sodium concentration for the saline-induced increase of neural firing was lower in SHR than in WKY. These findings demonstrate that basal activities and responsiveness to angiotensin II in AHA angiotensin II-sensitive neurons are enhanced in prehypertensive SHR as compared with age-matched WKY. In addition, these findings indicate that central saline-induced activation of AHA angiotensin II-sensitive neurons is also enhanced in SHR. It appears that the enhanced reactivity of SHR AHA neurons to angiotensin II occurs primarily in nature but not secondarily to raised blood pressure in SHR.

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. In the present study, we examined whether the AHA angiotensin II-sensitive neuron response to hypertonic saline would differ in SHR and Dahl S rats from those of their controls. Male 15- to 16-week-old SHR and age-matched Wistar Kyoto rats (WKY), Dahl S rats and Dahl R rats and Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Intracerebroventricular injection of hypertonic saline increased the firing rate of AHA angiotensin II-sensitive neurons. The threshold sodium concentration for the central sodium-induced increase of neural firing was lower in SHR than those of WKY, Dahl S rats, Dahl R rats and Wistar rats. The increase in neural firing induced by hypertonic saline (250 mM) was greater in SHR than those of other four kinds of rats. Similarly, the threshold sodium concentration was lower in Dahl S rats than those of WKY, Dahl R rats and Wistar rats and the increase in neural firing induced by hypertonic saline (250 mM) was greater in Dahl S rats than those of WKY, Dahl R rats and Wistar rats. In SHR, intracerebroventricular injection of the amiloride-sensitive sodium channel blocker benzamil abolished the hypertonic saline (250 mM)-induced increase in neural firing, but the sodium channel blocker itself did not affect the basal firing of these neurons. These findings indicate that central sodium-induced activation of AHA angiotensin II-sensitive neurons is enhanced in SHR and Dahl S 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. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Decreases in blood pressure induced by intravenous nitroprusside (100 ug/kg) increased the firing rate of AHA angiotensin II-sensitive neurons. The nitroprusside-induced increase of firing rate of AHA neurons was inhibited by PHN microinjection of the cholinoceptor antagonist scopolamine and potentiated by PHN microinjection of the cholinesterase inhibitor physostigmine. Microinjections of carbachol and glutamate into the PHN caused increases of firing rate of AHA neurons. The carbachol-induced but not glutamate-induced increase of unit firing was abolished by the pre-microinjection of scopolamine into the same sites of the PHN. These findings suggest that the nitroprusside-induced increase of firing of AHA neurons is mediated via acetylcholine at the level of the PHN.

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. In the present study, we examined whether the PHN cholinergic stimulation-induced activation of AHA angiotensin-II-sensitive neurons is altered in SHR. Male 15- to 16-week-old SHR and age-matched Wistar Kyoto rats (WKY) were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of the cholinoceptor agonist carbachol, the cholinesterase inhibitor physostigmine and the excitatory amino acid glutamate into the PHN caused increases in firing rate of AHA angiotensin-II-sensitive neurons in anesthetized WKY and SHR. The increase in firing rate of AHA neurons induced by these drugs was enhanced in SHR as compared to WKY. The enhancement of the physostigmine-induced activation of AHA neurons in SHR was similar to that of the carbachol-induced activation of AHA neurons in SHR. The enhancement of the glutamate-induced activation of AHA neurons in SHR was similar to that of the carbachol-induced activation of AHA neurons in SHR. Microinjection of scopolamine, a cholinoceptor antagonist, into the PHN caused a small but significant decrease of firing rate of AHA angiotensin-II-sensitive neurons in SHR but not in WKY. These findings indicate that the PHN cholinergic stimulation-induced activation of AHA angiotensin-II-sensitive neurons is enhanced in SHR and that PHN cholinergic mechanisms are involved in tonic activation of angiotensin-II-sensitive neurons in the AHA of SHR. It appears that the enhancement of the PHN cholinergic stimulation-induced activation of AHA neurons in SHR results mainly from the enhanced neural reactivity to angiotensins in AHA neurons of SHR.

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. In this study, we examined whether cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of carbachol, physostigmine and glutamate into the PHN caused an increase in firing rate of AHA angiotensin II-sensitive neurons in anesthetized rats. The carbachol-induced increase of firing rate was inhibited by pressure application of the AT1 receptor antagonist losartan onto AHA angiotensin II-sensitive neurons. The glutamate-induced increase of firing rate was also inhibited by the pressure application of losartan. PHN microinjections of carbachol and glutamate did not affect blood pressure in these anesthetized rats. In conscious rats, PHN microinjection of carbachol produced an increase of blood pressure and the carbachol-induced pressor response was inhibited by bilateral microinjections of losartan into the AHA. These findings indicate that cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. It seems likely that the activation of AHA angiotensin II-sensitive neurons induced by PHN cholinergic stimulation is partly mediated via release of angiotensins at AHA angiotensin II-sensitive neuron levels.

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. Extracellular potentials were recorded from single neurons in the AHA. Increases in blood pressure induced by intravenous phenylephrine completely inhibited the firing of AHA angiotensin II-sensitive neurons. The phenylephrine-induced inhibition of neuronal firing was blocked and enhanced by the pressure application of bicuculline and nipecotic acid, respectively, onto the same neurons. In contrast, decreases in blood pressure induced by intravenous nitroprusside increased the firing of angiotensin II-sensitive neurons. The nitroprusside-induced increase of neuronal firing was blocked by the pressure application of losartan onto the same neurons. These findings suggest that angiotensin II-sensitive neurons in the AHA respond to blood pressure changes via gamma-aminobutyric acid and angiotensins 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. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of carbachol into the LSV caused an increase in firing rate of AHA angiotensin II-sensitive neurons. The carbachol-induced increase of firing rate of AHA angiotensin II-sensitive neurons was inhibited by pressure application of the excitatory amino acid receptor antagonist kynurenate but not by the AT1 receptor antagonist losartan onto the same neurons. Microinjection of carbachol into the LSV also increased the firing rate of AHA ACh-sensitive neurons, and the carbachol-induced increase of firing rate of ACh-sensitive neurons was again abolished by pressure application of kynurenate but not by the muscarinic receptor antagonist scopolamine onto the same neurons. Microinjection of the muscarinic receptor antagonist 4-DAMP into the LSV did not affect the firing rate of AHA angiotensin II-sensitive neurons. These findings indicate that neurons in the LSV are involved in activation of AHA angiotensin II-sensitive neurons. It seems likely that the carbachol-induced activation of AHA angiotensin II-sensitive neurons is mainly mediated via excitatory amino acid receptors at AHA neurons.

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. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Intraventricular injection of hypertonic saline increased the neural activity of angiotensin II-sensitive neurons, whereas pressure application of hypertonic saline onto angiotensin II-sensitive neurons themselves did not affect their neural activities. The intraventricular hypertonic saline-induced increase of unit activity of AHA neurons was inhibited by pressure application of the angiotensin AT1 receptor antagonist losartan onto the same neurons. The hypertonic saline-induced increase of unit firing was also blocked by intraventricular injection of the amiloride-sensitive sodium channel blocker benzamil. In conscious rats, intraventricular injection of hypertonic saline produced pressor responses, and the hypertonic saline-induced pressor response was inhibited by bilateral microinjection of losartan into the AHA. Repeated intraventricular injection of hypertonic saline caused an increase in the release of angiotensins in the AHA of anesthetized rats. These findings indicate that intracerebroventricular injection of hypertonic saline increases neural activity of angiotensin II-sensitive neurons trans-synaptically via endogenous angiotensins in the AHA. In addition, these findings also indicate that the intracerebroventricular injection of hypertonic saline produces a pressor response at least partly via release of angiotensins in the AHA.

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. Male 15- to 16-week-old SHR and age-matched Wistar-Kyoto rats (WKY) and Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Pressure application of the PKC activator phorbol 12-myristate 13-acetate (PMA) onto angiotensin II-sensitive neurons in the AHA of Wistar rats increased their firing rate. The increase of unit activity by PMA was inhibited by the potent inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), but not by the weak PKC inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004). The increase of unit firing by PMA was enhanced in SHR as compared with WKY. Pressure application of H-7 alone decreased the basal firing activity of angiotensin II-sensitive neurons in SHR but not in WKY. HA1004 did not affect the basal firing activity of angiotensin II-sensitive neurons in SHR. Angiotensin II-induced increases of firing rate in AHA neurons were inhibited by H-7 and the inhibition by H-7 was enhanced in SHR as compared with WKY. Pressure application of 4-aminopyridine, a blocker of the transient potassium current, onto angiotensin II-sensitive neurons increased their firing rate and the increase of unit firing rate was almost the same in WKY and SHR. These findings indicate that activation of PKC increases neural activity in angiotensin II-sensitive neurons in the AHA and that this PKC activation-induced increase of neural activity is enhanced in the AHA of SHR. It seems likely that the enhanced PKC activation effect is responsible for the enhanced basal neural activity seen in the AHA of SHR.

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. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of glutamate into the MeA caused an increase in the firing rate of AHA angiotensin II-sensitive neurons. The glutamate-induced increase of firing rate was inhibited by pressure application of the AT1 receptor antagonist losartan onto AHA angiotensin II-sensitive neurons. The microinjection of glutamate into the central amygdaloid area also increased the firing rate of AHA angiotensin II-sensitive neurons, but the glutamate-induced increase of firing rate was not affected by pressure application of losartan onto AHA angiotensin II-sensitive neurons. The microinjection of corticotropin-releasing factor (CRF) into the MeA also increased the firing rate of AHA angiotensin II-sensitive neurons, but the CRF-induced increase of firing rate was not inhibited by pressure application of losartan onto AHA angiotensin II-sensitive neurons. Repeated microinjection of glutamate into the MeA caused an increase in the release of angiotensins in the AHA. These findings indicate that neurons in the MeA are involved in the activation of AHA angiotensin II-sensitive neurons. It seems likely that the activation of AHA angiotensin II-sensitive neurons induced by glutamate but not CRF is partly mediated via the release of angiotensins at AHA angiotensin II-sensitive neuron levels.

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). Male 15- to 16- or 6-week-old SHR and age-matched WKY were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Pressure application of angiotensin II onto some neurons in the AHA increased their firing rate. The basal firing rate of angiotensin II-sensitive neurons was increased in both 15- to 16- and 6-week-old SHR than in age-matched WKY. The increase of unit firing by angiotenisn II was enhanced in both 15- to 16- and 6-week-old SHR as compared with age-matched WKY. Pressure application of losartan, an angiotensin type 1 (AT1) receptor antagonist, alone decreased the basal firing rate of angiotensin II-sensitive neurons in 15- to 16-week-old SHR and WKY. The decrease of unit firing by losartan was also enhanced in SHR as compared with WKY. Pressure application of glutamate onto angiotensin II-sensitive neurons increased their firing rate and the increase of unit firing by glutamate was enhanced in 15- to 16-week-old SHR as compared with age-matched WKY. These findings suggest that activities of angiotensin II-sensitive neurons in the AHA are enhanced in SHR as compared with WKY. It is possible that the enhanced activity of angiotensin II-sensitive neurons in the AHA of SHR is partly due to enhanced neuronal reactivity to angiotensin II.

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. Extracellular potentials were recorded from single neurons in the AHA. Pressure-ejected application of angiotensin II and glutamate onto some neurons in the AHA increased their firing rate. The increase of unit firing induced by angiotensin II but not by glutamate was inhibited by losartan. Application of losartan alone inhibited the basal firing rate of angiotensin II-sensitive neurons in a concentration-dependent manner. Application of the angiotensin AT2 receptor antagonist, PD123319, did not affect the increase of unit firing induced by angiotensin II and the basal firing rate of angiotensin II-sensitive neurons. Pressure application of angiotensin I onto angiotensin II-sensitive neurons also increased firing rate and the increase of unit firing by angiotensin I was inhibited by the angiotensin converting enzyme inhibitor, captopril. Captopril alone inhibited the basal firing rate of angitensin II-sensitive neurons. Acetylcholine did not affect unit firing of angiotensin II-sensitive neurons, whereas it increased the firing rate of some angiotensin II-insensitive neurons in the AHA. Increases of blood pressure by intravenous phenylephrine completely inhibited the basal firing rate of angiotensin II-sensitive neurons. These findings suggest that some neurons in the AHA are tonically activated by endogenous angiotensins. It seems likely that newly synthesized angiotensins are used for the angiotensinergic transmission in the AHA.

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. Injections of a fluorescent tracer into the LSV produced maximal retrograde labeling within the LSD. Microinjection of carbachol (10-100 pmol) into the LSD produced a dose-dependent pressor response. The pressor response to carbachol was inhibited by microinjection of muscimol (80 pmol) or 4-DAMP (1 nmol) into the ipsilateral side of the LSV. Microinjection of muscimol (80 pmol) into the LSD also inhibited the pressor response induced by restraint stress. Repeated injections of carbachol (30 pmol) into the LSD produced Fos immunoreactivity in the ipsilateral side of the LSV. These findings suggest that the LSD projects to the LSV and that these projections may be involved in blood pressure increase.

Central angiotensin systems are involved in expression of pressor responses induced by immobilization stress. In this study, we examined whether angiotensin receptors in the anterior hypothalamic area are involved in the pressor response during stress exposure in rats. Intracerebroventricular injections of the angiotensin AT1-receptor antagonist losartan (6.5 and 22 nmol) attenuated pressor responses to immobilization stress dose-dependently. Injections of losartan (0.065 and 0.22 nmol) into the anterior hypothalamic area also suppressed the stress-induced pressor response dose-dependently, whereas intraventricular injection of losartan (2.2 nmol) did not affect it. Immobilization stress caused increases in plasma catecholamine levels. The stress-induced increase of plasma catecholamine levels was also inhibited by angiotensin receptor blockade in the anterior hypothalamic area. The present results suggest that angiotensin receptors in the anterior hypothalamic area are involved in expression of the pressor response and sympathetic activation induced by immobilization stress.

The rostral ventrolateral medulla (RVLM) has cholinergic mechanisms responsible for pressor responses. Stimulation of the hypothalamic paraventricular nucleus (PVN) causes an increase of arterial pressure via activation of neurons in the RVLM. In this study, we examined whether PVN stimulation causes a pressor response via activation of cholinergic mechanisms in the RVLM. Male Wistar rats were used and they were anesthetized, paralyzed and artificially ventilated. Electrical stimulation of the PVN produced a pressor response. Microinjection of the muscarinic receptor antagonist scopolamine and the cholinesterase inhibitor physostigmine into the RVLM inhibited and potentiated, respectively, the pressor response induced by PVN stimulation. PVN stimulation also increased the firing rate of RVLM barosensitive neurons and the increase in the firing rate was inhibited and potentiated by scopolamine and physostigmine, respectively, iontophoretically applied on neurons. Microinjection of L-glutamate into the PVN produced a release of ACh in the RVLM. The inhibitory amino acid gamma-aminobutyric acid injected into the lateral parabrachial nucleus (LPBN) inhibited the pressor response induced by PVN stimulation. These results suggest that PVN stimulation causes an increase in arterial pressure via activation of cholinergic inputs in the RVLM. It appears that the pressor response is mediated, at least in part, via cholinergic inputs from the LPBN.

We examined whether sites in the lateral parabrachial nucleus (PBN) where L-glutamate produced increases in arterial pressure were involved in mediation of cholinergic inputs to neurons in the rostral ventrolateral medulla (RVLM). Male Wistar rats were anesthetized, paralyzed and artificially ventilated. Unilateral microinjection of L-glutamate into the lateral PBN produced a pressor response. Microinjection of the muscarinic receptor antagonist scopolamine into the unilateral RVLM inhibited the pressor response to L-glutamate injected ipsilaterally into the lateral PBN, whereas microinjection of the cholinesterase inhibitor physostigmine into the RVLM enhanced it. PBN microinjection of L-glutamate also enhanced the firing rate of RVLM sympathoexcitatory neurons and the enhancement of the firing rate was inhibited by scopolamine iontophoretically applied on neurons. PBN injection of L-glutamate produced a tetrodotoxin (TTX)-sensitive release of ACh in the RVLM. Unilateral microinjection of TTX into the lateral PBN inhibited the pressor response induced by RVLM microinjection of physostigmine. These results provide evidence that neurons in the pressor sites of the lateral PBN are involved in mediation of cholinergic inputs responsible for pressor responses in the RVLM.