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Vol. 285, Issue 3, 1012-1018, June 1998
Institute of Pharmacology, University of Kiel, Kiel, Germany (F.Q., T.W., A.W., S.H., T.U.) and Department of Pediatrics, University of Giessen, Giessen, Germany (W.R.)
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Abstract |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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We studied the involvement of periventricular and hypothalamic angiotensinergic and cholinergic pathways in osmotically induced arginine vasopressin (AVP) release into the blood. In conscious Wistar rats, i.c.v. injections of 0.2, 0.3 and 0.6 M hyperosmolar saline (5 µl) resulted in concentration-dependent increases in AVP release (5.2 ± 1.5, 10.6 ± 2.2 and 18.0 ± 2.2 pg/ml, respectively, vs. 2.0 ± 0.1 in controls). The two lower saline concentrations did not affect arterial blood pressure (non-pressure-associated AVP release), whereas 0.6 M saline induced increase in blood pressure (pressure-associated AVP release). In the first set of experiments, periventricular angiotensin AT1, muscarinic or nicotinic receptors were blocked by i.c.v. administration of losartan (10 nmol), atropine (100 nmol) or hexamethonium (100 nmol), respectively, before i.c.v. hyperosmolar saline injections. Losartan significantly reduced the 0.2 M and 0.3 M, but not the 0.6 M, saline-induced increase in AVP release. The 0.3 M saline-induced AVP release was blocked by atropine and hexamethonium, whereas the 0.6 M saline-induced AVP release was blocked by atropine only. In the second set of experiments, losartan (4 nmol), atropine (200 nmol) or hexamethonium (200 nmol) was injected bilaterally into the paraventricular nucleus before i.c.v. hyperosmolar saline injections. Losartan reduced 0.3 M and potentiated 0.6 M saline-induced AVP release. On the other hand, atropine and hexamethonium significantly reduced both 0.3 and 0.6 M saline-induced AVP release. We conclude that afferents arising from periventricular osmosensitive neurons to the hypothalamic paraventricular nucleus, which are involved in non-pressure-associated osmotically induced AVP release, are both angiotensinergic and cholinergic, whereas those mediating pressure-associated AVP release are cholinergic in nature.
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Introduction |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Blood-borne
signals such as plasma hypernatremia and an increase in ANG II act on
osmo/sodium or angiotensin receptors found in CVOs, such as the SFO and
the OVLT, that are known to be involved in osmoregulation. Stimulation
of these receptors in CVO activates neural pathway(s) that project to
the hypothalamic PVN and SON, which results in increased release of AVP
into the circulation (Miselis 1982
; Furguson and Kasting 1986; Gutman
et al., 1988). The chemical nature of the neuronal pathways
that influence the release of AVP has not been fully established. Up to
now, two of these pathways have been characterized that project
directly to the PVN and SON: a noradrenergic afferent pathway arising
from A1, A2 and A6 adrenergic cell groups in the brain stem
(Sawchenko and Swanson, 1983; Wilkin et al., 1989) and
angiotensinergic projections arising from the SFO (Lind et
al., 1985; Wilkin et al., 1989 and Oldfield et
al., 1991). The contribution of adrenergic and angiotensinergic inputs to the control of AVP release has been investigated by many
authors. In recent studies, we demonstrated that stimulation of
periventricular angiotensin receptors in normotensive Wistar rats
induced a dose-dependent increase in NA release in the anterior hypothalamic region (Qadri et al., 1991), in the PVN
(Stadler et al., 1992) and in the SON (Qadri et
al., 1993), along with an increase in plasma AVP levels. Further,
we characterized the nature of the adrenoceptors and angiotensin
receptors in the PVN and SON involved in i.c.v. ANG II-induced AVP
release: a1- and a2-adrenergic and AT1 receptors within the PVN
(Veltmar et al., 1992) and a1-adrenergic and AT1 receptors
within the SON (Qadri et al., 1993). We also showed in these
studies that ANG II stimulates the release of NA, which, in turn, by
acting on a1- and a2-adrenoceptors located on the magnocellular
neurons, mediates the release of AVP.
Besides ANG II and catecholamines, central ACh is believed to be an
important neurotransmitter mediating AVP release (Bhargava et
al., 1972; Gregg, 1985; Yamaguchi and Hama, 1989). It has been demonstrated that hyperosmolar saline, when applied peripherally, affected the electrical activity of neurosecretory cells in the PVN and
that the effect of hyperosmolar saline was blocked by pretreatment with
(Sar1, Ala8]-ANG II, atropine and
hexamethonium, the respective angiotensinergic, muscarinic and
nicotinic cholinergic receptor antagonists (Akaishi and Negoro, 1983).
These data suggest the involvement, in osmotically induced AVP release,
of angiotensinergic as well as cholinergic receptor mechanisms in the
PVN. In addition, water deprivation and local changes in osmolarity in
the PVN resulted in an increased release of ANG II and ANG III within
this nucleus (Harding et al., 1992; Qadri et al.,
1994). Taken together, these data imply the participation of central
angiotensinergic and cholinergic systems in the control of body fluid
homeostasis via the release of AVP.
The present experiments were designed to examine specifically the
contribution of periventricular and hypothalamic angiotensinergic and
cholinergic mechanisms to AVP release in response to central osmotic
stimulation by i.c.v. injections of hyperosmolar saline. We chose the
hypothalamic PVN to study the involvement of the angiotensinergic and
cholinergic systems in osmotically induced AVP release because neurons
from the PVN respond to small increases in extracellular osmolarity
with a marked increase in their firing rate (Akaishi and Negoro, 1983;
Gutman et al., 1988). Further, a single i.p. injection of
hyperosmolar saline caused not only an increased firing rate but also
changes in neuronal morphology in the PVN (Beagley and Hatton, 1994).
Furthermore, the PVN contains angiotensinergic and cholinergic
innervations and receptors (Hatton and Mason, 1985; Imboden et
al., 1989, 1992; Lind et al., 1985; Oldfield et
al., 1989; Obermüller et al., 1991; Pow and
Morris, 1989).
In the first part of the study, angiotensinergic AT1 or cholinergic receptor antagonists were administered i.c.v. before the i.c.v. injections of hyperosmolar saline. In the second part of the study, angiotensinergic or cholinergic receptor antagonists were administered bilaterally into the PVN before i.c.v. saline injections.
Our data demonstrate that both angiotensinergic and cholinergic pathways are involved in PVN-mediated AVP release and, further, that the individual recruitment of these pathways depends on the strength of the osmotic signal.
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Materials and Methods |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Animals
Male Wistar rats weighing 300 to 350 g were obtained from Dr. Karl Thomae GmbH (Biberach/Riss, Germany). The animals were kept under controlled temperature, humidity and light/dark period (0600 h on, 1800 h off) and were allowed free access to food (Altromin standard rat diet, 0.2% sodium) and water.
Implantation of Chronic Intracerebral Guide Cannulas for the Microinjection of Drugs into the PVN
Rats were anesthetized with chloralhydrate (400 mg/kg b.w.,
i.p.). Intracerebral guide cannulas were implanted bilaterally 2 mm
above the PVN with a Kopf-stereotaxic apparatus. The guide cannulas
were fashioned from 21-gauge stainless steel tubing and fitted with
indwelling stylets. They were secured to the skull with two stainless
steel screws and dental cement as described earlier (Veltmar et
al., 1992). According to the rat brain atlas by Paxinos and Watson
(1986), the coordinates for PVN were 1.5 mm caudal to the bregma, 0.7 mm lateral to the midline and 5.5 mm ventral to the dural surface.
Injections into the PVN were performed using a 31-gauge stainless steel
tubing that extended 2.0 mm beyond the tip of the intracerebral guide
cannula
7.5 mm below the dural surface. Besides the implantation of
the guide cannulas into the PVN, a polypropylene cannula was inserted
into the lateral brain ventricle as described earlier (Unger et
al., 1981).
One week after implantation of the i.c.v. cannula and intracerebral guide cannulas, a polypropylene catheter for blood sampling was placed in the right femoral artery under chloralhydrate anesthesia. The catheter was filled with heparinized physiological saline, sealed, exteriorized and secured at the nape of the neck. Experiments were started 24 hr after implantation of the femoral catheter.
Experimental Protocols
Involvement of periventricular angiotensinergic and cholinergic receptors in AVP release in response to i.c.v. hyperosmolar saline. Protocol 1: Animals received i.c.v. hyperosmolar saline injections of 0.2, 0.3 or 0.6 M. Ninety seconds later, 1 ml of blood was drawn from the left femoral artery to measure plasma AVP levels. Blood volume was substituted i.a. with 1 ml of isotonic saline. In all experiments, 0.15 M isotonic saline was used for control i.c.v. injections.
Protocol 2: The specific angiotensin AT1 receptor antagonist losartan (10 nmol) was injected i.c.v. 5 min before i.c.v. 0.2, 0.3 or 0.6 M saline injection. Ninety seconds later, 1 ml of blood was drawn from the left femoral artery to measure plasma AVP levels as described in protocol 1. The dose of losartan was sufficient to block periventricular AT1 receptors completely (Veltmar et al., 1992; Qadri et al., 1993).
Protocol 3: The specific muscarinic receptor antagonist
atropine (100 nmol) or the nicotinic receptor antagonist hexamethonium (100 nmol) was injected i.c.v. 5 min before i.c.v. 0.3 or 0.6 M saline
injection. Ninety seconds later, 1 ml of blood was drawn from the left
femoral artery to measure plasma AVP levels. The doses of the
cholinergic receptor antagonists were chosen on the basis of previously
published data (Akaishi and Negoro 1983; Iitake et al.,
1986).
Contribution of angiotensinergic and cholinergic receptors in the PVN to AVP release in response to i.c.v. hyperosmolar saline. Protocol 4: Losartan (4 nmol) was injected bilaterally into the PVN 10 min before i.c.v. 0.3 or 0.6 M saline injections. Ninety seconds later, 1 ml of blood was drawn from the left femoral artery to measure plasma AVP levels.
Protocol 5: The muscarinic receptor antagonist atropine (200 nmol) or the nicotinic receptor antagonist hexamethonium (200 nmol) was injected bilaterally into the PVN 10 min before i.c.v. 0.3 or 0.6 M saline injection. Ninety seconds later, 1 ml of blood was drawn from the left femoral artery to measure plasma AVP levels. The doses of atropine, hexamethonium and losartan were chosen on the basis of previously published data (Akaishi and Negoro, 1983; Iitake et
al., 1986; Veltmar et al., 1992; Qadri et
al., 1993).
Verification of Microinjection Location
After completion of the experiments, animals were sacrificed. Pontamine sky blue solution (200 nl) (Gurr BDH, U.K.) was injected bilaterally into the PVN. Then brains were removed, kept in 10% formaldehyde for at least 5 days and sectioned to verify the correct localization of the microinjections. Only data from animals in which the microinjection needle was correctly placed in the PVN were processed (table 1).
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Drugs and Chemicals
Losartan was a gift from Dr. R. Smith, DuPont-Merck, Wilmington,
DE; atropine and hexamethonium were purchased from Sigma (München, Germany). All drugs were dissolved in isotonic saline and kept in 20-ml aliquots at 
20°C until used. Different
concentrations of hyperosmolar saline were prepared freshly in
distilled water for each experiment.
Drug Administration
Different concentrations of hyperosmolar saline solutions (0.2, 0.3 or 0.6 M) were injected i.c.v. in a total volume of 5 µl/60 sec and flushed with 3 µl of isotonic saline. Angiotensinergic or cholinergic receptor antagonists were microinjected into the PVN in a volume of 200 nl/60 sec.
Different concentrations of hyperosmolar saline were injected into the lateral brain ventricle in random order. Separate groups of animals were used in each individual set of experiments. Each animal received at most two different concentrations of saline injected on separate days (experimental protocols 2, 3, 4 and 5). Only the animals in experimental protocol 1 were treated with different concentrations of saline on separate days for 4 days. The time interval between individual injections into the lateral brain ventricle or PVN was at least 24 to 48 hr (table 1).
AVP Assay
Plasma AVP levels were measured by radioimmunoassay after
acetone extraction as described previously (Rascher et al.,
1981).
Statistical Analyses
Data are expressed as mean ± S.E.M. Statistical analysis was performed using one-way repeated-measures ANOVA followed by post-hoc comparison of individual groups with Bonferroni's test when appropriate. A significance level of P < .05 was accepted.
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Results |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Effect of i.c.v. hyperosmolar saline injections on mean arterial BP and on AVP release into the circulation. I.c.v. injections of 0.2 and 0.3 M saline had no effect on systemic blood pressure, whereas 0.6 M saline induced an increase in blood pressure (n = 4) (fig. 1). Basal plasma AVP levels in unrestrained Wistar rats were 1.82 ± 0.08 pg/ml (n = 9). The i.c.v. injection of isotonic saline had no effect on plasma AVP levels (2.39 ± 0.36 pg/ml, n = 9). Hyperosmolar saline injected i.c.v. at concentrations of 0.2, 0.3 (non-pressure-associated) and 0.6 M (pressure-associated) increased AVP release in a concentration-dependent fashion (fig. 2).
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Effect of periventricular angiotensin AT1 receptor blockade on i.c.v. hyperosmolar saline-induced AVP release. Blockade of periventricular AT1 receptors by i.c.v. administration of losartan (10 nmol) significantly inhibited the 0.2 M and 0.3 M saline-induced AVP release, whereas the 0.6 M saline-induced AVP release showed a tendency to increase upon losartan pretreatment (fig. 3). The i.c.v. administration of losartan followed by i.c.v. isotonic saline (control group) had no effect on basal AVP release (table 2).
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Effect of periventricular muscarinic or nicotinic receptor blockade on i.c.v. hyperosmolar saline-induced AVP release. Blockade of periventricular muscarinic receptors by i.c.v. administration of atropine (100 nmol) inhibited both 0.3 M and 0.6 M saline-induced AVP release, whereas blockade of periventricular nicotinic receptors with hexamethonium (100 nmol) inhibited only 0.3 M but not 0.6 M saline-induced AVP release (fig. 4). In control experiments, i.c.v. injections of atropine or hexamethonium followed by i.c.v. isotonic saline did not affect basal plasma AVP levels (table 2).
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Effect of angiotensin AT1 receptor blockade in the PVN on i.c.v. saline-induced AVP release. Losartan (4 nmol) injected bilaterally into the PVN reduced 0.3 M saline-induced, but increased 0.6 M saline-induced, AVP release (fig. 5). In control experiments, bilateral administration of losartan into the PVN followed by i.c.v. isotonic saline did not affect plasma AVP levels (table 2).
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Effect of blockade of cholinergic (muscarinic and nicotinic) receptors in the PVN on i.c.v. hyperosmolar saline-induced AVP release. Atropine (200 nmol) and hexamethonium (200 nmol) injected bilaterally into the PVN inhibited both 0.3 and 0.6 M saline-induced AVP release (fig. 6). In control experiments, bilateral microinjections of atropine or hexamethonium into the PVN followed by isotonic saline did not affect basal plasma AVP levels (table 2).
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Discussion |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Involvement of periventricular angiotensinergic and cholinergic receptors in osmotically induced AVP release. In the present study, we were able to differentiate between 1) central mechanisms of AVP release involved in acute, moderate increases in osmolality (produced by i.c.v. injections of 0.2 and 0.3 M saline) without changes in BP and 2) mechanisms involved in acute, drastic increases in osmolality (produced by 0.6 M saline) accompanied by changes in BP. Administration of hyperosmolar saline into the lateral brain ventricle elicited a concentration-dependent increase in plasma AVP levels. Pretreatment with atropine significantly reduced the effect of both non-pressure-associated (0.3 M saline) and pressure-associated (0.6 M saline) release of AVP. On the other hand, pretreatment with hexamethonium or losartan reduced only the effect of non-pressure-associated AVP release in response to hyperosmolar saline. These data suggest that cholinergic (muscarinic and nicotinergic) and angiotensinergic pathways are activated in non-pressure-associated osmotically induced AVP release, whereas only muscarinic cholinergic pathways are activated in pressure-associated osmotically induced AVP release.
Our findings are compatible with data published recently by Rohmeiss et al. (1995a, b) on the effect of subpressor and pressor concentrations of hyperosmolar saline on natriuresis in conscious normotensive rats. Intracerebroventricular injections of a low concentration of hyperosmolar saline (0.23 M) induced an increase in
natriuresis without influencing mean arterial BP. This effect, as in
the case of osmotically induced AVP release in the present study, was
mediated via periventricular AT1 receptors (Rohmeiss et al., 1995a) as well as AT1 receptors found in the
osmosensitive subfornical organ (Rohmeiss et al., 1995b).
Further, the natriuresis associated with the increase in mean arterial
BP induced by i.c.v. injections of 0.6 M saline was unaffected by
i.c.v. pretreatment with losartan. These data, together with the
present findings, suggest a common central pathway between osmotically
induced AVP release and natriuresis in response to low or high
concentrations of hyperosmolar saline.
We have previously calculated that CSF osmolality is increased by about
0.5% and 1.6% after the i.c.v. injection of 5 µl of 0.2 and 0.3 M
saline solution, respectively (Höhle et al., 1996). Regardless of cholinergic receptor specificity, our findings imply that
small changes in extracellular osmolarity after i.c.v. hyperosmolar saline administration induce the release of ACh as a neurotransmitter. These findings further suggest that in the chain of events, an interneuron situated between the periventricular osmoreceptor and the
AVP-secreting cell in hypothalamic magnocellular neurons releases ACh
across the cholinergic synapses, resulting in AVP secretion into the
blood. In the present experiments, stimulation of periventricular
osmoreceptors by hyperosmolar saline may have induced ACh release in
the hypothalamic nuclei in both non-pressure-associated and
pressure-associated AVP release. In addition to ACh, angiotensin peptides are also involved in the non-pressure-associated AVP release,
because 0.2 and 0.3 M saline-induced AVP release was inhibited by
i.c.v. pretreatment with the AT1 receptor antagonist losartan.
Angiotensin may function directly as a neurotransmitter or indirectly
as a neuromodulator influencing ACh in the hypothalamic nuclei. It has
been shown that ANG II can induce ACh release in the peripheral nervous
system (McCubbin 1974) and the CNS (Elie and Panniset, 1970). Thus, in
the present experiments, angiotensinergic afferents may have affected
the cholinergic system in the hypothalamic nuclei.
In contrast to the data presented here, Yamaguchi and Hama (1989)
reported that neither i.c.v. ANG II- nor hyperosmolar saline-induced AVP release was affected by i.c.v. pretreatment with atropine or
hexamethonium, whereas carbachol-induced AVP release was inhibited by
atropine but not by hexamethonium, which suggesting that ACh is not
involved in ANG II- or hyperosmolar saline-induced AVP release. The
discrepancies between our and their data could be explained in two
ways: 1) Yamaguchi and Hama used only pressure-associated hyperosmolar
saline concentrations, whereas we differentiated between
non-pressure-associated and pressure-associated hyperosmolar saline
concentrations. 2) The dose of atropine used in their study may not
have been high enough to inhibit cholinergic pathways involved in
angiotensin- and osmotically induced AVP release, although it was
obviously sufficient to inhibit the effect of exogenously applied
carbachol (28 nmol vs. 100 nmol in our study). Further, in
our study we did observe an inhibitory effect of i.c.v. hexamethonium
in non-pressure-associated but not in pressure-associated osmotically
induced AVP release.
On the other hand, our findings are in agreement with those of previous
investigators who reported that cholinergic agents, such as carbachol
and ACh, act centrally to stimulate AVP release via
muscarinic rather than nicotinic receptors (Bhargava et al., 1972; Hoffman, 1979; Hatzikostas et al., 1980; Iitake
et al., 1986), results that support our present in
vivo observations that stimulation of periventricular
osmoreceptors with hyperosmolar saline may trigger ACh release, which
acts on postsynaptic muscarinic receptors to induce an increase in AVP
release.
It is obvious that the exact site(s) of action of cholinergic and/or
angiotensinergic afferent mechanisms in osmotically induced AVP release
cannot be determined when the antagonists are applied i.c.v., because
afferents from periventricular organs reach both the PVN and SON and
can stimulate them simultaneously. Therefore, in the second part of our
study we investigated whether angiotensinergic and/or cholinergic
mechanisms within the hypothalamic PVN are involved in the osmotically
induced release of AVP.
Contribution of angiotensinergic and cholinergic receptors in the PVN to AVP release in response to i.c.v. saline. The data in the present study provide in vivo evidence that AVP release after stimulation of periventricular osmoreceptors is mediated via angiotensinergic and cholinergic (muscarinic and nicotinic) receptors in the PVN. We were able to differentiate possible mechanisms involved in non-pressure-associated and pressure-associated hyperosmolar saline-induced AVP release induced by low (0.3 M) and high (0.6 M) concentrations of hyperosmolar saline, respectively. We found that stimulation of periventricular osmoreceptors with low concentrations of hyperosmolar saline involves angiotensinergic receptors and muscarinic and nicotinic cholinergic receptors in the hypothalamic PVN, whereas stimulation of osmoreceptors with high concentrations of hyperosmolar saline involves only muscarinic and nicotinic cholinergic receptors, but not angiotensinergic receptors, in the PVN.
In a parallel study, we observed that blockade of muscarinic receptors in the hypothalamic SON inhibited, whereas nicotinic receptors potentiated, the non-pressure-associated and pressure-associated osmotically stimulated release of AVP (Waldmann et al., 1994). On the other hand, in the present study, blockade of muscarinic and nicotinic receptors in the PVN inhibited both the
non-pressure-associated and the pressure-associated osmotically
stimulated AVP release. The apparent discrepancy between the role of
muscarinic and nicotinic receptors in the PVN and in the SON may be due
to the heterogeneity of neurosecretory cells within the PVN. A
plausible explanation for the discrepancy may be that in the PVN, both
muscarinic and nicotinic receptors are facilitatory, whereas in the
SON, muscarinic receptors are facilitatory and nicotinic receptors
inhibitory in nature. The inhibitory and stimulatory receptors can be
located on the same neuron. The concept of a balance between nicotinic and muscarinic receptors in not new (Gregg, 1985). Furthermore, several
authors have reported that there are both nicotinic and muscarinic
receptors in the PVN facilitating AVP release (Moss et al.,
1972; Michels et al., 1986; Okuda et al., 1993).
Our findings are consistent with those of previous investigators who
reported that an intracarotid injection of 0.6 M NaCl increased the
firing rate of neurosecretory cells in the PVN. The firing rate of 60%
of cells stimulated by hyperosmolar saline was blocked by local
application of hexamethonium into the PVN, 80% after atropine
pretreatment and 40% after the angiotensin antagonist saralasin
(Akaishi and Negoro 1983). Thus our present data and the findings of
Akaishi and Negoro both suggest the involvement of cholinergic and
angiotensinergic mechanisms in osmotically induced AVP release.
One discrepancy between our present data and those reported by Akaishi
and Negoro is that we observed an involvement of angiotensin AT1
receptors on non-pressure-associated (0.3 M saline), but not on
pressure-associated (0.6 M saline), osmotically stimulated AVP release.
It is possible that in their study, 0.6 M saline introduced into the
carotid artery was already diluted before it reached the
periventricular osmoreceptors. Therefore, the effect of 0.6 M saline
given peripherally may be comparable to the low concentrations of
saline (0.2 or 0.3 M) in the present study where the hyperosmolar
saline was applied directly into the brain ventricle.
At this point, we are unable to explain the potentiating effect of
losartan pretreatment on 0.6 M saline-induced AVP release. It is
possible that 0.6 M saline given i.c.v. stimulated angiotensinergic pathways toward PVN as well as SON and that there is a cross-talk between PVN and SON. Blockade of AT1 receptors in the PVN may have
stimulated the angiotensinergic system in the SON and hence the
potentiated increase in AVP levels in the blood. Another possibility is
that blockade of AT1 receptors within the PVN unmasked the facilitatory
effect of AT2 receptors. In a previous study, we found that blockade of
periventricular AT2 receptors with PD 123177 via the i.c.v.
route reduced the 0.6 M, but enhanced the 0.2 M, saline-induced release
of AVP (Höhle et al., 1996). This suggests that
periventricular AT2 receptors, unlike the AT1 receptors, may suppress
non-pressure-associated, but facilitate pressure-associated, osmotically induced AVP release. The role of AT2 receptors within the
hypothalamic PVN in osmotically stimulated AVP release needs to be
further investigated in view of discrepant reports demonstrating the
presence (Obermüller et al., 1991) and the absence of
AT2 receptors in the PVN (Jöhren et al., 1996; Lenkei
et al., 1996; Reagan et al., 1996).
In summary, a moderate increase in osmolality in the CFS
(non-pressure-associated) stimulates periventricular osmoreceptors found on osmosensitive circumventricular neurons. This may lead to an
increased release of ACh and angiotensin across synapses in the
hypothalamus. ACh, in turn, by acting on postsynaptic muscarinic and
nicotinic receptors, and angiotensin, by acting on postsynaptic AT1
receptors in the PVN, both stimulate receptor-mediated release of AVP.
A large increase in CSF osmolality (pressure-associated) also
stimulates periventricular osmoreceptors found in the CVO leading to
what may be a predominant ACh release across synapses in the PVN. ACh
acting on muscarinic and nicotinic receptors found on magnocellular
neurons in the PVN stimulates AVP release from the neurohypophysis. The
contribution of angiotensinergic pathways to pressure-associated
hyperosmolar saline-induced AVP release remains to be investigated.
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Acknowledgment |
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The authors wish to thank Mrs. Ursula Jakobs, Department of Pediatrics, University of Giessen, Germany, for performing the vasopressin radioimmunoassay.
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Footnotes |
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Accepted for publication February 2, 1998.
Received for publication August 4, 1997.
1 This work was supported by a grant-in-aid from the Deutsche Forschungsgemeinschaft (DFG) Un 47/2-3 and Zi 10/22-1. F. Qadri was a recipient of a doctorate scholarship from the Deutsche Forschungsgemeinschaft (DFG) - Graduiertenkolleg "Experimentelle Nierenund Kreislaufforschung."
Send reprint requests to: Fatimunnisa Qadri, Ph.D., Institute of Pharmacology, Medical University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
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Abbreviations |
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AVP, arginine vasopressin; PVN, paraventricular nucleus; SON, supraoptic nucleus; CVO, circumventricular organs. BP, blood pressure; ANG II, angiotensin II; SFO, subfornical organ; OVLT, organum vasculosum of the lamina terminalis; NA, nonadrenaline.
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References |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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