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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.

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.

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.

Previously, we demonstrated that the rostral part of the ventral zone of the lateral septal area (LSV) was involved in the restraint stress-induced pressor response. It is suggested that there exist acetylcholine receptors responsible for blood pressure increase in the caudal part of the lateral septal area. In this study, we examined whether acetylcholine receptors responsible for pressor responses also exist in the rostral part of the LSV and whether these acetylcholine receptors are involved in the stress-induced pressor response in rats. Microinjection of either carbachol (10-100pmol) or physostigmine (0.46 and 1.5nmol) into the LSV caused a dose-dependent increase in blood pressure. The pressor response to carbachol (30pmol) was inhibited by the M1 antagonist pirenzepine and the M3 antagonist 4-DAMP mustard but not by the M2 antagonist methoctramine injected into the LSV. Bilateral microinjections of the M1/M3 antagonist 4-DAMP (1nmol) inhibited the restraint stress-induced pressor response. These findings suggest that M1/M3 muscarinic receptors responsible for blood pressure increase exist in the rostral part of the LSV and they are partly involved in the stress-induced pressor response.