Increases In Arginine Vasopressin Secretion Research Articles

Bimatoprost Ophthalmic Solution (BOS) 0.3 mg w/v for 1 Open Trial of Long-term Preventive Therapy of Migraine in 3 patients with Pathophysiologic Shift from Brain to Eye

Known since antiquity, migraine is a complex primary disorder, an episodic painful Autonomic Nervous System (ANS) storm, generally following the stress/post-stress phase. Despite exhaustive study of neuropeptides, neurochemicals, molecules, neurogenetics, neuroimaging along with animal and human experiments over the last 50 years, the scientific basis of migraine remains unknown. Straddling eight decades from Cortical Spreading Depression (CSD) to Calcitonin-Gene Related Peptide (CGRP) and its antagonists, exponentially increasing data have failed to create a gestalt synthesis. This article lays cohesive and robust fundamental principles for the comprehension and management of migraine. The continuum between migraine and non-congestive Primary Open-Angle Glaucoma (POAG), Normal Tension Glaucoma (NTG), or Low-Tension Glaucoma (LTG) is advancing. The case of sustained remission of migraine attacks (> 75%) over 3 years - 5 years with ocular hypotensive topical Bimatoprost Ophthalmic Solution (BOS) 0.3% in an N-of-1 trial in 3 patients with refractory migraine is presented. A cause-effect-adaptive process underlies the ANS-stress/post-stress-linked biology of migraine. Vasopressin-serotonin-norepinephrine ‘homeostatic-adaptive system’ Lowers Intraocular Pressure (IOP), while enhancing anti-stress, antinociception, vasomotor, and behaviour control functions, thereby selectively decreasing algogenic neural traffic in the ophthalmic division of trigeminal nerve (V1), and, raising the threshold to develop migraine. Striking migraine headache-aborting feature of vomiting is also likely linked to a several hundred-fold increase in arginine-vasopressin secretion. Eye-cover tests and self-ocular digital displacement are essential to studying the visual aura. Real-time physical displacement of Scintillating Scotoma (SS) and floating ‘stars’ is reported. The basis of spontaneous onset and offset, self-limited duration of migraine attacks, as well as female preponderance, and age/menopause decline in prevalence, are elucidated. Intraocular implants with long-term ocular hypotensive effects, including bimatoprost, are the future of migraine management. Controlled trials are required to establish the migraine-preventive effect of topical bimatoprost, a revolutionary advance in neuroscience.

Arginine Vasopressin and Posterior Reversible Encephalopathy Syndrome Pathophysiology: the Missing Link?

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by a typical brain edema. Its pathogenesis is still debated through hypoperfusion and hyperperfusion theories, which have many limitations. As PRES occurs almost exclusively in clinical situations with arginine vasopressin (AVP) hypersecretion, such as eclampsia and sepsis, we hypothesize that AVP plays a central pathophysiologic role. In this review, we discuss the genesis of PRES and its symptoms through this novel approach. We theorize that AVP axis stimulation precipitates PRES development through an increase in AVP secretion or AVP receptor density. Activation of vasopressin V1a receptors leads to cerebral vasoconstriction, causing endothelial dysfunction and cerebral ischemia. This promotes cytotoxic edema through hydromineral transglial flux dysfunction and may increase endothelial permeability, leading to subsequent vasogenic brain edema. If our hypothesis is confirmed, it opens new perspectives for better patient monitoring and therapies targeting the AVP axis in PRES.

Serum Vasopressin Response in Patients With Intradialytic Hypotension

Arginine vasopressin (AVP), an endogenous hormone with vasopressor properties, may be inadequately secreted during episodes of intradialytic hypotension (IDH). To evaluate this, we performed a prospective, observational pilot study of 20 chronic hemodialysis patients assessing the baseline AVP level and trend of AVP with ultrafiltration in patients with a diagnosis of IDH compared with patients without IDH. Ten symptomatic IDH patients and 10 controls were enrolled and matched for age, gender, and dialysis vintage. AVP levels were obtained hourly throughout the dialysis session and during hypotensive episodes. We observed that IDH patients experienced greater decreases in both systolic and diastolic blood pressure during the dialysis session despite equivalent ultrafiltration in both groups. AVP concentration did not increase in the IDH patients (5.0 +/- 1.8) compared with controls (6.4 +/- 6.0) (P = 0.5) despite hypotensive events. This study suggests that symptomatic IDH patients are unable to mount an appropriate increase in AVP secretion in the setting of hypotension. These findings support the possibility of AVP as a mechanism driven therapy for patients with symptomatic IDH.

Mechanisms of centrally administered ET-1-induced increases in systemic arterial pressure and AVP secretion.

Endothelins (ET) within the central nervous system (CNS) alter systemic cardiovascular responses and arginine vasopressin (AVP) secretion. These experiments were designed to ascertain whether the rise in systemic arterial pressure after central administration of ET-1 is mediated by enhancing sympathetic outflow and/or circulating AVP. In Long-Evans (LE/LE) rats, intracerebroventricular injection of 1-10 pmol ET-1 dose dependently increased mean arterial pressure (MAP). Peak response occurred 7-12 min after ET-1 and was inhibited by ETA receptor antagonism. Systemic vasopressin (V1) receptor blockade did not inhibit the pressor response, and rats with central diabetes insipidus (DI/DI) displayed an identical rise in MAP. Ganglionic blockade prevented ET-1-induced hemodynamic effects. Peak plasma AVP levels occurred 60 min after ET-1, as the pressor response began to wane. In sinoaortic-denervated LE/LE rats, ET-1 elicited a 10-fold increase in AVP secretion that coincided with the hemodynamic changes and was blocked by BQ-123. Thus ET-1 via ETA receptors within the CNS induced a concentration-dependent increase in systemic arterial pressure mediated by enhanced sympathetic outflow but not by circulating AVP. Reflex baroreceptor activation attenuated AVP release.

Development of concentration thresholds for fetal swallowing and arginine vasopressin stimulation in the preterm ovine fetus

We previously demonstrated that fetal swallowing was stimulated by intracarotid saline injections in the near term (130 ± 1 days gestation) ovine fetus. In order to examine the ontogeny of the regulation of thirst-mediated swallowing behavior and arginine vasopressin (AVP) secretion, the present study examined fetal swallowing and AVP secretory responses to hypertonic NaCl and sucrose in preterm (115 days gestation) ovine fetuses. Five fetuses were chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyogram (EMG) electrodes, an esophageal flow probe, and vascular catheters. Fetuses received intracarotid injections (0.15 ml/kg) of increasing concentrations of NaCl (0.15–2.55 M), administered at 2-min intervals. The threshold saline concentration for swallowing was defined as the minimum NaCl dose eliciting swallow responses (within 20 s) following 4 of 5 injections at each dose. In 2 fetuses, the threshold dose was 0.75 M (confirmed by 4 of 5 injections resulting in swallows at the next higher dose). In the other 3 animals, no swallowing threshold was observed (i.e., no dose through 2.55 M elicited swallows to 4 of 5 injections). There were no significant increases in AVP secretion. On a subsequent day, equimolar sucrose injections did not affect fetal swallowing activity or AVP secretion. Together with previous reports, these studies indicate that plasma osmolality dipsogenic mechanisms become functional in some ovine fetuses by 115 days gestation, while all fetuses exhibit intact osmotic dipsogenic responses at 130 days gestation. These results further suggest an acute process of development of dipsogenic responsiveness, rather than by gradually increasing sensitivity to osmotic stimuli. © 1996 Wiley-Liss, Inc.

Development of concentration thresholds for fetal swallowing and arginine vasopressin stimulation in the preterm ovine fetus

We previously demonstrated that fetal swallowing was stimulated by intracarotid saline injections in the near term (130 +/- 1 days gestation) ovine fetus. In order to examine the ontogeny of the regulation of thirst-mediated swallowing behavior and arginine vasopressin (AVP) secretion, the present study examined fetal swallowing and AVP secretory responses to hypertonic NaCl and sucrose in preterm (115 days gestation) ovine fetuses. Five fetuses were chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyogram (EMG) electrodes, an esophageal flow probe, and vascular catheters. Fetuses received intracarotid injections (0.15 ml/kg) of increasing concentrations of NaCl (0.15-2.55 M), administered at 2-min intervals. The threshold saline concentration for swallowing was defined as the minimum NaCl dose eliciting swallow responses (within 20 s) following 4 of 5 injections at each dose. In 2 fetuses, the threshold dose was 0.75 M (confirmed by 4 of 5 injections resulting in swallows at the next higher dose). In the other 3 animals, no swallowing threshold was observed (i.e., no dose through 2.55 M elicited swallows to 4 of 5 injections). There were no significant increases in AVP secretion. On a subsequent day, equimolar sucrose injections did not affect fetal swallowing activity or AVP secretion. Together with previous reports, these studies indicate that plasma osmolality dipsogenic mechanisms become functional in some ovine fetuses by 115 days gestation, while all fetuses exhibit intact osmotic dipsogenic responses at 130 days gestation. These results further suggest an acute process of development of dipsogenic responsiveness, rather than by gradually increasing sensitivity to osmotic stimuli.

The Effect of Acute Exercise on the Secretion of Corticotropin-Releasing Factor, Arginine Vasopressin, and Adrenocorticotropin as Measured in Pituitary Venous Blood from the Horse

We have used the technique which we have developed for collecting pituitary venous blood from conscious, undisturbed horses to study the effect of acute vigorous exercise on the secretion of CRF, arginine vasopressin (AVP) and ACTH. Pituitary venous (pit) blood was collected every 1-5 min from nine trained racehorses at rest in the stable. The horses then trotted quietly for 10 min, after which they galloped as fast as possible for 4-6 min, before returning to the stable where sampling continued. In Exp 1 (n = 5) no blood samples were taken during exercise, whereas in Exp 2 (n = 4), pit blood was collected every 30 sec during exercise. Immediately after exercise, significant elevations in heart rate (P less than 0.001), body temperature (P less than 0.01) and hematocrit (P less than 0.001) were observed as compared with preexercise values. Jugular cortisol levels were higher after exercise (301.9 +/- 35.2 nmol/liter; mean +/- SEM) than before (187.3 +/- 34.8; P less than 0.01; n = 9). Likewise, jugular AVP levels increased with exercise (before, 0.65 +/- 0.11 pmol/liter; after 3.2 +/- 0.6; P less than 0.01; n = 6), whereas jugular CRF was not altered by exercise (before, 0.38 +/- 0.08 pmol/liter; after, 0.93 +/- 0.31; n = 6; NS). In Exp 1, no significant changes in pit ACTH, AVP, or CRF were observed after exercise. However in Exp 2 when pit blood was sampled during exercise all horses showed an immediate and dramatic rise in ACTH (P less than 0.01) and AVP (P less than 0.005) secretion which peaked during galloping with mean fractional changes above resting levels of 23.6 +/- 9.9 for ACTH and 51.7 +/- 24.0 for AVP. After exercise pit AVP levels were not different from resting, whereas ACTH remained elevated (11.4 +/- 6.9-fold above resting levels). By contrast, pit CRF levels were not altered by exercise. In both experiments together, pit AVP and ACTH concentrations were correlated in eight of the nine horses, whereas pit CRF and ACTH concentrations were positively correlated in only one of seven horses. We conclude that acute exercise causes a transient increase in ACTH secretion which occurs synchronously with an increase in AVP secretion. CRF does not appear to play a major role in mediating the initial ACTH response to exercise.

Inhibition of elevated arginine vasopressin secretion in response to osmotic stimulation and acute haemorrhage by U‐62066E, a κ‐opioid receptor agonist

1. The effect of kappa (kappa) opioid receptor activation on the increase in arginine vasopressin (AVP) secretion evoked by two acute and quite different stimuli (i.e., haemorrhage and osmotic stimulus due to hypertonic saline infusion) were evaluated in conscious Long-Evans rats, by use of U-62066E, a highly selective kappa-opioid receptor agonist, and MR2266, an opioid receptor antagonist with some selectivity for kappa-receptors. 2. An acute haemorrhage, which reduced the mean blood pressure by approximately 50%, resulted in a large increase in the plasma AVP (pAVP) levels of control rats. However, the administration of U-62066E (0.2 mg kg-1 or 2.0 mg kg-1) reduced the increase due to haemorrhage in a dose-dependent manner. In contrast, concomitant administration of 2.0 mg kg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 2.0 mg kg-1. 3. Hypertonic saline infusion (5% hypertonic saline solution at a rate of 0.24 ml kg-1 min-1 for 10 min) caused the elevation of plasma osmolality (pOsm) from 294.0 +/- 1.6 mosmol kg-1 to 304.4 +/- 1.9 mosmol kg-1, simultaneously resulting in a significant increase in pAVP levels from 2.34 +/- 0.28 pg ml-1 to 4.54 +/- 0.51 pg ml-1. However, the administration of U-62066E (0.05 mg kg-1 or 0.2 mg kg-1) reduced the osmotically induced increase in pAVP in a dose-dependent manner although pOsm showed the same degree of increase as in controls. In contrast, concomitant administration of 0.2mgkg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 0.2mgkg- , whereas pOsm showed the same degree of increase as in controls. No significant changes in the mean blood pressure of the respective groups were observed during this experiment. 4. It is suggested that the Kappa-Opioid receptor activation reduces the increase in AVP secretion evoked by these two different stimuli and that the inhibitory involvement occurs in the neural lobe in the process of AVP secretion.

Effect of isolation stress on concentrations of arginine vasopressin, alpha-melanocyte-stimulating hormone and ACTH in the pituitary venous effluent of the normal horse.

A non-surgical, non-stressful technique was used for collection of pituitary venous blood from five conscious horses every minute for two 10-min periods before and during isolation from the herd, which caused a predictable, yet humane and physiological, emotional stress. Pituitary blood was also sampled every 5 min for two approximately 90-min periods before and after isolation, while jugular blood was sampled every 15 min throughout the experiment. During isolation, all horses became agitated, hyperventilating and sweating. Packed red cell volume increased, as did pituitary venous concentrations of adrenaline (mean +/- S.E.M. concentration before isolation, 621.5 +/- 112.3 pmol/l; peak during isolation, 2665.4 +/- 869.8 pmol/l; P less than 0.05) and noradrenaline (before, 871.8 +/- 111.8 pmol/l; peak, 2726.1 +/- 547.4 pmol/l; P less than 0.02). Concentrations of arginine vasopressin (AVP) were higher in pituitary venous but not in jugular blood during isolation than during the preceding 10-min period (P less than 0.05). Although AVP secretion increased in all horses, in three of the five it rose dramatically in the first minute of isolation to 25.7 (horse 1), 13.6 (horse 4) and 145.1 (horse 5) times the level in the last sample collected before isolation. Mean pituitary venous concentrations of ACTH and alpha-MSH increased during isolation in the three horses which had large increases in AVP secretion, but, overall, stress did not significantly affect ACTH or alpha-MSH secretion. Similarly, mean jugular cortisol levels were not significantly altered by isolation. However, the magnitudes of ACTH, AVP and alpha-MSH responses to isolation were negatively correlated with the jugular cortisol level before isolation. The changes in pituitary venous concentrations of ACTH and AVP were synchronous under resting conditions, whether samples were collected at intervals of 1 (P less than 0.01) or 5 (P less than 0.005) min; however, this synchrony was lost during isolation. The changes in pituitary venous concentrations of ACTH and alpha-MSH were synchronous both at rest (P less than 0.025 for 1-min sampling, P less than 0.01 for 5-min sampling) and during isolation (P less than 0.01). We conclude that isolation stress increases AVP secretion and may alter the temporal relationship between pituitary venous concentrations of AVP and ACTH. Furthermore, the magnitude of the responses of AVP, ACTH and alpha-MSH to isolation is significantly affected by the prevailing cortisol level.

The effect of aging on neurohypophyseal function

In healthy adults, secretion of the antidiuretic hormone, arginine vasopressin (AVP), is controlled largely by osmotic hemodynamic variables. Osmoregulation is mediated via neurons located in the anterior hypothalamus near but distinct from the neurosecretory cells. By some unknown mechanism, this osmostat is able to detect and respond to very small changes in the plasma concentration of sodium and certain other solutes. The sensitivity of this system varies considerably from person to person but is constant on repeat testing in a given subject. With advancing age, however, the sensitivity of the osmoregulatory system appears to increase progressively. Thus, by the sixth decade, the amount of AVP released per unit increment in plasma osmalality is about twice that secreted by subjects in the third decade. Whether this age related enhancement is due to increased sensitivity of the osmostat per se or to increased neurohypophyseal stores of AVP has not been determined. Aging also appears to affect the baroregulation of AVP but in the opposite direction. Whereas healthy young adults subjected to moderate hypovolemia and/or hypotension invariably exhibit pronounced increases in AVP secretion, the same or a greater hemodynamic stimulus evokes no AVP response in almost half of all subjects over 68 years of age. The lack of AVP response is not due to detects in the neurohypophysis or baroreceptor per se because osmotically mediated AVP release and orthostatically induced catecholamine release are normal to super normal in healthy elderly subjects. Thus, the age related defect in baroregulation probably is located in one or more pathways between the vasomotor center and neurohypophysis. Preliminary data suggests it is associated with abnormalities in the control of basal and orthostatic blood pressure and may also be linked to the age related change in osmoregulatory function. The predilection of elderly subjects to disorders of salt and water balance may be due in part to these age related alterations in neurohypophyseal regulation.

Vincristine Neurotoxicity and Abnormal Secretion of Antidiuretic Hormone

The secretion of the antidiuretic hormone, arginine vasopressin, has been studied in a patient who developed peripheral neuropathy and the syndrome of inappropriate antidiuresis during therapy with vincristine sulfate. The patient's plasma arginine vasopressin concentration, determined by a radioimmunoassay technique, was markedly increased despite profound hyponatremia and rose even higher following correction of the electrolyte imbalance. In six other vincristine-treated patients, in whom neither neuropathy nor inappropriate antidiuresis was observed, plasma arginine vasopressin concentration was in the normal range. These findings indicate that the inappropriate antidiuresis, which can occur during vincristine therapy, is associated with an abnormal increase in arginine vasopressin secretion. This complication appears to be related to the other neurotoxic effects of the drug and may be due to an alteration in the normal osmoreceptor control of vasopressin secretion.