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. 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.     

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. 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.     

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. 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.     

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. 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.     

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. 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.     

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). 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.     

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. 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.     

Cardiovascular effects produced by microinjection of angiotensins and angiotensin antagonists into the ventrolateral medulla of freely moving rats

In this study we determined the cardiovascular effects produced by microinjection of angiotensin peptides [Angiotensin-(1–7) and Angiotensin II] and angiotensin antagonists (losartan, L-158,809, CGP 42112A, Sar¹-Thr⁸-Ang II, A-779) into the rostral ventrolateral medulla of freely moving rats. Microinjection of angiotensins (12.5–50 pmol) produced pressor responses associated to variable changes in heart rate, usually tachycardia. Unexpectedly, microinjection of both AT₁ and AT₂ ligands produced pressor effects at doses that did not change blood pressure in anesthetized rats. Conversely, microinjection of Sar¹-Thr⁸-Ang II and the selective Ang-(1–7) antagonist, A-779, produced a small but significant decrease in MAP an HR. These findings suggest that angiotensins can influence the tonic activity of vasomotor neurons at the RVLM. As previously observed in anesthetized rats, our results further suggest a role for endogenous Ang-(1–7) at the RVLM. The pressor activity of the ligands for AT₁ and AT₂ angiotensin receptor subtypes at the RVLM, remains to be clarified.     

Central injection of galanin inhibits angiotensin II-induced responses in rats

Galanin inhibits electrical activation of angiotensin II-sensitive neurons in the subfornical organ, which is related to angiotensin II-induced drinking behavior and pressor responses. In this study, the authors investigated whether intracerebroventricular injection of galanin in conscious rats inhibits the responses. Water intake following intracerebroventricular injection of angiotensin II at 100 pmol was inhibited significantly by coinjection of galanin at over 25 pmol, although galanin alone did not affect water intake. Furthermore, angiotensin II-induced pressor responses were inhibited significantly by coinjection of galanin at 50 pmol while galanin alone elicited slight pressor responses. These results suggest that galanin inhibits angiotensin II-induced physiological responses.     

Activation of hypothalamic angiotensin receptors produces pressor responses via cholinergic inputs to the rostral ventrolateral medulla in normotensive and hypertensive rats

We have previously reported that the angiotensin system in the anterior hypothalamic area (AHA) is enhanced in spontaneously hypertensive rats (SHR) and that this enhancement is involved in hypertension in SHR. In addition, acetylcholine (ACh) release is increased in the rostral ventrolateral medulla (RVLM) of SHR, which has also been shown to be involved in hypertension in SHR. In this study, we examined whether the enhanced angiotensin system in the AHA of SHR is related to the increase in cholinergic inputs to the RVLM. Electrical stimulation in the AHA produced a pressor response and an increase in firing rate of RVLM barosensitive neurons. These responses were inhibited and enhanced by RVLM application of the muscarinic receptor antagonist scopolamine and the cholinesterase inhibitor physostigmine, respectively. AHA stimulation also produced release of ACh in the RVLM. Microinjections of angiotensin II and carbachol into the AHA produced pressor responses. The pressor response to angiotensin II was inhibited by scopolamine microinjected into the RVLM, although this produced no effect on the response to carbachol. In SHR, although not in Wistar-Kyoto rats, microinjection of losartan into the AHA inhibited pressor responses to physostigmine. However inhibition was not observed in response to the directly acting muscarinic receptor agonist carbachol, injected into the RVLM. These findings demonstrate that angiotensin receptor activation or electrical stimulation in the AHA produce a pressor response via an increase in ACh release in the RVLM. In addition, the present study suggests that the enhanced angiotensin system in the AHA of SHR increases cholinergic inputs to the RVLM, which leads to increases in blood pressure.     

Angiotensinergic pathway through the median preoptic nucleus in the control of oxytocin secretion and water and sodium intake

Our objective was to study in which situations the median preoptic nucleus (MnPO) interferes with the control of oxytocin secretion and salt intake and the possible mediation of angiotensin II (AII) through their AT1 receptors. Lesion of the MnPO by ibotenic acid in male rats did not change water and NaCl intake in conditions of ad libitum offer, water deprivation or salt load, but it did cause significant decrease of NaCl intake in sodium depleted animals. These animals presented higher water intake or lower NaCl intake after microinjection of AII or losartan into the MnPO, respectively. They decreased plasma oxytocin after microinjection of losartan into the MnPO, but not of AII or isotonic saline. Oxytocin secretion induced by hypertonic saline i.p. was reduced by microinjection of AII, but not losartan into the MnPO. On the other hand, microinjection of losartan in this area, but not AII, reduced plasma oxytocin in animals submitted to the isotonic saline i.p. Thus, it seems that the sodium intake control is performed by MnPO neurons through the stimulatory action of angiotensin II on AT1 receptors under sodium depletion, but not water deprivation or salt overload neither of ad libitum water and salt intake condition. On the other hand, in the high-sodium condition, endogenous angiotensin did not act on MnPO neurons to the control of oxytocin secretion while exogenous angiotensin inhibited oxytocin secretion. These results indicate two possible angiotensinergic neural circuits: one is stimulating and the other is inhibiting oxytocin secretion, depending on sodium balance.     

Angiotensin receptor blockade in the anterior hypothalamic area inhibits stress-induced pressor responses in rats

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.     

An angiotensin system in the anterior hypothalamic area anterior is involved in the maintenance of hypertension in spontaneously hypertensive rats

An overactive brain renin-angiotensin system is one of the factors contributing to the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). We examined brain sites where enhanced activity of an angiotensin system is responsible for the pathogenesis of hypertension in SHR. The angiotensin receptor antagonist, losartan was injected into tissues around rostral parts of the third ventricle in conscious rats. Losartan (0.22 nmol) injected into the anterior hypothalamic area, anterior (AHA) produced a depressor response in SHR but not in Wistar Kyoto rats (WKY). Angiotensin II (0.091-0.91 pmol) injected into the AHA produced a pressor response in both WKY and SHR, and the pressor response to angiotensin II was greater in SHR than that of WKY. Carbachol (3 pmol) injected into the AHA also produced a pressor response in WKY and SHR, and the pressor response to carbachol was almost the same in both strains of rats. Release of angiotensin peptides in the AHA was greater in SHR than that of WKY. These findings suggest that an angiotensin system in the AHA is enhanced and this enhancement of angiotensin system is involved in the maintenance of hypertension in SHR. Both increased pressor reactivity to angiotensin II and increased release of angiotensin peptides in the AHA appear to be related to this enhancement of angiotensin system in SHR.     

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. 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.     

Midbrain central gray is involved in mediation of cholinergic inputs to the rostral ventrolateral medulla of the rat

There are cholinergic inputs responsible for pressor responses in the rostral ventrolateral medulla (RVLM) and stimulation of midbrain central gray (CG) increases arterial pressure via activation of neurons in the RVLM. In this study, we examined whether the CG was involved in mediation of the cholinergic inputs to the RVLM. Male Wistar rats were anesthetized, paralyzed, and artificially ventilated. Unilateral microinjection of L-glutamate into the CG 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 CG, whereas microinjection of the cholinesterase inhibitor physostigmine into the RVLM enhanced it. CG stimulation also enhanced the firing rate of RVLM barosensitive neurons and the enhancement of the firing rate was inhibited by scopolamine iontophoretically applied on neurons. CG injection of L-glutamate produced a release of acetylcholine in the RVLM. Unilateral microinjection of L-glutamate into the pedunculopontine tegmental nucleus (PPT) also produced a pressor response, but the pressor response to L-glutamate was not affected by scopolamine injected ipsilaterally into the RVLM. These results provide evidence that the CG but not the PPT is involved in mediation of cholinergic inputs responsible for pressor responses in the RVLM.     

Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis in the rat

We evaluated the role of endogenous angiotensins at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of spontaneous baroreceptor reflex (BRR) response and the subtype of angiotensin receptors involved using rats anesthetized and maintained with pentobarbital sodium. Bilateral microinjection of angiotensin II (ANG II) or its active metabolite angiotensin III (ANG III) (5, 10, or 20 pmol) into the NRVL significantly suppressed the spontaneous BRR response, as represented by the magnitude of transfer function between systemic arterial pressure and heart rate signals. The inhibitory effect of ANG III (20 pmol) was discernibly reversed by coadministration with its peptide antagonist, [Ile(7)]ANG III (1.6 nmol), or the nonpeptide AT(2) receptor antagonist, PD-123319 (1.6 nmol), but not by the nonpeptide AT(1) receptor antagonist, losartan (1.6 nmol). On the other hand, the peptide antagonist, [Sar(1), Ile(8)]ANG II (1.6 nmol) or both non-peptide antagonists appreciably reversed the suppressive action of ANG II (20 pmol). Whereas losartan produced minimal effect, blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of PD-123319, [Sar(1), Ile(8)]ANG II or [Ile(7)]ANG III elicited significant enhancement of the spontaneous BRR response. We conclude that under physiologic conditions both endogenous ANG II and ANG III may exert a tonic inhibitory modulation on the spontaneous BRR response by acting selectively on the AT(2) subtype receptors at the NRVL.     

Role of Anterior Peri-Third Ventricular Structures in the Regulation of Supraoptic Neuronal Activity and Neurohypophysical Hormone Secretion in the Rat

Neurohypophysical hormone release, and the electrical activity of single neurons of the supraoptic nucleus, were monitored in urethane-anaesthetized rats. Immediately after electrolytic lesions of the region anterior and ventral to the third ventricle (AV3V region), supraoptic neurons showed little spontaneous activity and their responses to ip injection of hypertonic saline were severely impaired; corresponding deficits were found in the secretion of both oxytocin and vasopressin. Similar deficits in oxytocin secretion were also found in rats following electrolytic lesions which destroyed all or part of the subfornical organ; however the effects of the lesions were not additive: rats with lesions of both the AV3V region and the subfornical organ region showed a similar degree of impairment of osmotically stimulated oxytocin secretion to rats with lesions of either site alone. Such deficits might occur either as a result of destruction of osmoresponsive projections to the magnocellular nuclei, or as a result of destruction of an afferent input which is essential for the full expression of the innate osmosensitivity of supraoptic neurons. To test the latter possibility, supraoptic neurons in AV3V-lesioned rats were activated by continuous application of glutamate, and then tested with ip injection of hypertonic saline. Five of seven cells tested responded significantly to the hyperosmotic stimulus, though the responses were significantly weaker than observed in sham-lesioned rats. We suggest that the innate osmosensitivity of supraoptic neurons does contribute to their responses to systemic osmotic stimulation, but that expression of this innate osmosensitivity requires inputs from the AV3V region and/or the subfornical organ, some of which may also be osmoresponsive. Electrical stimulus pulses applied to the AV3V region influenced the electrical activity of most supraoptic neurons strongly: the predominant response was a short-latency, short-duration inhibition followed by long-latency, long-duration excitation. Whereas intracerebroventricular administration of the angiotensin II antagonist saralasin reduced spontaneous or osmotically induced activity of supraoptic neurons, the neuronal responses to AV3V stimulation were impaired only with relatively high doses of saralasin. We conclude that angiotensin ll-sensitive neurons are an important component of the afferent pathways that sustain the excitability of supraoptic neurons, but that angiotensin is probably not the major transmitter of the projection from the AV3V region to the supraoptic nucleus.     

Evaluation for roles of periventricular cholinoceptors in vasopressin secretion in response to angiotensin II and an osmotic stimulus

In conscious rats, intracerebroventricular (i.c.v.) injections (10 microliters) of carbachol (1.4 nmol), angiotensin II (AII; 48.2 pmol) or a hypertonic solution (990 mOsm/kg) produced increases of plasma vasopressin (AVP) and arterial pressure. The effects of carbachol were inhibited not by a nicotinic cholinergic blocker hexamethonium (28 nmol), but by a muscarinic cholinergic blocker atropine (28 nmol). However, neither hexamethonium nor atropine affected the AVP and pressor responses to AII or the hypertonic solution. We concluded that periventricular cholinoceptors may not be involved in the central actions of AII and hypertonicity on AVP release and blood pressure.     

Effects of glucagon-like peptide-1 (7-36) amide on neurohypophysial hormone secretion induced by acute hyperosmotic challenge

This study was designed to investigate possible effects of glucagon-like peptide-1 (7-36) amide on the vasopressin and oxytocin release induced by acute peripheral or central osmotic stimulation. In the first series of experiments, rats were injected intraperitoneally with the isotonic (0.15 M) or hypertonic (1.5 M) NaCl solution and then, intracerebroventricularly, with either 1 microg glucagon-like peptide-1 (7-36) amide dissolved in 5 microl of isotonic saline or with the vehicle only. In the second study, 1 microg glucagon-like peptide-1 (7-36) amide, dissolved in isotonic or hypertonic (0.6 M) saline, was injected into the cerebroventricular system. Control rats were treated with isotonic or hypertonic saline only. All the animals were decapitated 10 min after the intracerebroventricular injection. Glucagon-like peptide-1 (7-36) amide enhanced significantly the basal secretion of vasopressin and oxytocin. Moreover, this peptide increased additionally the release of both neurohypophysial hormones stimulated previously by peripheral osmotic challenge. On the other hand, the peptide increased the oxytocin but not vasopressin secretion brought about by an intracerebroventricular injection of hypertonic saline thus suggesting that the central osmotic stimulation decreases the sensitivity of vasopressin neurons to glucagon-like peptide-1 (7-36) amide. It is concluded that glucagon-like peptide-1 (7-36) amide may affect the secretory activity of the hypothalamo-neurohypophysial system under acute osmotic challenge.     

Chemosensitivity of neurons in the dorsal motor nucleus of the vagus that responded to portal infusion of hypertonic saline in rats

Neural responses in the dorsal motor nucleus of the vagus (DMV) to topical administrations of sodium and portal infusions of hypertonic saline were investigated electrophysiologically by using multibarrel electrodes in anesthetized rats. Of 102 neurons that showed antidromic response to electrical stimulation of the ventral gastric vagus or the accessory celiac vagus, 51 neurons increased and 13 neurons decreased their discharge rates in response to the electrophoretic administration of sodium. The other 38 neurons did not respond to this stimulation. The portal infusion of hypertonic saline elicited neural responses of some DMV neurons whose axons are involved into either the ventral gastric or the accessory celiac vagus. Further, effects of the topical administration and the portal infusion of hypertonic saline were examined on 33 neurons. Typical response was characterized by an increase in discharge rate responding to both of the portal infusion and the topical administration. In conclusion, the DMV neurons receiving the afferent inputs from hepatoportal osmoreceptors may have an enteroceptor function detecting the change in osmotic pressure of their environment.