Prostacyclin as neuromodulator in the sympathetically stimulated rabbit heart

Prostaglandin E2 (PGE2) has previously been shown to inhibit sympathetic neurotransmission in different organs and species. Based on this inhibitory effect and on its reversal by cyclo-oxygenase inhibitors, PGE2 has been claimed to be a physiological modulator of in vivo release of norepinephrine (NE) from sympathetic nerves. It is now recognized that prostacyclin (PGI2) is the main cyclo-oxygenase product in the heart. We therefore addressed the question whether PGI2, within the same preparation, is formed in increased amounts during sympathetic nerve stimulation and has neuromodulatory activity. The effluent from isolated rabbit hearts subjected to sympathetic nerve stimulation or to infusion of NE or adenosine (ADO) was collected, and its content of PGE2 and 6-keto-PGF1 alpha (dehydration product of PGI2) was analyzed using gas chromatography/mass spectrometry, operated in the negative ion/chemical ionization mode. Other hearts were infused with PGI2 and nerve stimulation induced outflow of endogenous NE into the effluent was analyzed using HPLC with electrochemical detection. Nerve stimulation at 5 or 10 Hz (before but not after adrenergic receptor blockade), as well as infusion of NE (10(-6)-10(-5)M) or ADO (10(-4)M) increased the cardiac outflow of 6-keto-PGF1 alpha. Basal and nerve stimulation induced efflux of 6-keto-PGF1 alpha was approximately 5 times higher than the corresponding efflux of PGE2. PGI2 dose-dependently inhibited the outflow of NE from sympathetically stimulated hearts, the inhibition at 10(-6)M being approximately 40%. On the basis of these observations we propose that PGI2 is a more likely candidate than PGE2 as a potential modulator of neurotransmission in cardiac tissue in vivo.     

Endogenous endothelin attenuates the pressor response to acute environmental stress via the ETA receptor

Clinical studies have documented an abrupt rise in plasma endothelin-1 (ET-1) coincident with an increase in mean arterial pressure (MAP) during the response to acute stress. We therefore examined the ET(A) and ET(B) receptor-dependent effects of ET-1 on the pressor response to acute environmental stress in ET-1-dependent hypertension. Stress was induced by administration of air jet pulses (3 min) in ET(B) receptor-deficient (ET(B) sl/sl) rats fed normal salt (NS; 0.8% NaCl), high salt (HS; 8% NaCl), and HS plus the ET(A) receptor antagonist ABT-627 (5 mg.kg(-1).day(-1)) on successive weeks. MAP was chronically monitored by telemetry. Total pressor response (area under the curve) was significantly reduced in ET(B) sl/sl rats maintained on a HS vs. NS diet [-6.8 mmHg (SD 18.7) vs. 29.3 mmHg (SD 8.1) x 3 min, P < 0.05]. Conversely, the total pressor response was augmented in both wild-type [34.2 mmHg (SD 29.2) x 3 min, P < 0.05 vs. NS] and ET(B) sl/sl rats [49.1 mmHg (SD 11.8) x 3 min, P < 0.05 vs. NS] by ABT-627. Blockade of ET(B) receptors in Sprague-Dawley rats caused an increase in basal MAP that was enhanced by HS and lowered by mixed ET(A)/ET(B) receptor antagonism; none of these treatments, however, had any effect on the pressor response. These data demonstrate that increasing endogenous ET-1 suppresses the pressor response to acute stress through ET(A) receptor activation in a genetic model of ET-1-dependent hypertension. These results are consistent with reports that ET-1 can attenuate sympathetically mediated responses.     

Effects of indomethacin and PGE1 on the vasoconstrictor responses of the rabbit ear artery to nerve stimulation.

Actions of PGE1 and indomethacin on electrically induced vasoconstriction in isolated ear arteries of rabbits were studied. PGE1 (8.5 X 10(-9) M) reduced the vasoconstriction; this inhibition was inversely related to the rate of stimulation. Indomethacin (1.5 X 10(-6) M) potentiated the constrictor responses to nerve stimulation. The degree of this potentiation was also frequency-dependent being greater at low (1 - 2 HZ) than at high (8 - 16 HZ) rate of stimulation. These findings support the view that prostaglandins, in addition to their action on vascular smooth muscle cells, play a functional role in the regulation of tone of the rabbit ear artery by a negative feed-back control of adrenergic neurotransmission.     

Prostaglandins do not mediate the inhibitory effects of angiotensins II and III on autonomic neurotransmission in the rabbit vas deferens

The role of prostaglandins in mediating angiotensin effects on autonomic neurotransmission was assessed. This was accomplished by examining the angiotensin-induced production of prostaglandins (PGE) and suppression of non-adrenergic (purinergic) neurotransmission in the presence and absence of cyclo-oxygenase inhibitors. The vas deferens of the rabbit was utilized for these studies because this preparation has a predominant non-adrenergic neurogenic component. Both angiotensins II and III enhanced PGE production and reduced non-adrenergic neurogenic contractions in a concentration-dependent manner from 1 to 1000 nM. Furthermore, indomethacin (2.8 microM) and eicosatetraynoic acid (10 microM) eliminated the inhibitory effect of the angiotensins on non-adrenergic neurotransmission. However, acetylsalicylic acid (10 microM) prevented the production of PGE in response to the angiotensins but failed to alter the suppression of non-adrenergic neurotransmission. The latter data are inconsistent with the hypothesis that PG's mediate angiotensin-induced depression of non-adrenergic neurotransmission. The mechanism by which indomethacin and eicosatetraynoic acid prevent angiotensin effects on non-adrenergic neurotransmission was not elucidated but previous reports suggest that these agents may act as angiotensin receptor antagonists. All of the cyclo-oxygenase inhibitors examined tended to potentiate angiotensin effects on adrenergic neurotransmission.     

Functional compartmentalization of arginine-vasopressin-activated cyclic AMP in anterior pituitary gland: the presence of a compartment activated by prostaglandin E2

AVP(10(-8)-10(-6)M) increased ACTH as well as PGE2 release from rat anterior pituitary quarters in vitro in a concentration dependent manner. IBMX (0.1 mM), a phosphodiesterase inhibitor, increased the ACTH response to AVP. The cAMP content in pituitary tissue was increased by AVP. Cyclooxygenase inhibition by indomethacin(1.4 X 10(-5) M) or diclofenac (1.8 X 10(-5)M) led to a potentiation of AVP-evoked ACTH secretion and to a decrease in AVP-stimulated cAMP formation. PGE2(10(-6)M) significantly increased pituitary cAMP content and indomethacin did not affect cAMP levels activated by PGE2. PGE2 attenuated the AVP-induced ACTH release. These results indicate that at least two functional compartments of AVP-activated cAMP responses are involved in the AVP-induced ACTH release. One compartment is directly activated by AVP and participates in the propagation of AVP-induced ACTH release. The second compartment is activated by PGE2. The contribution of the second compartment to the regulation of ACTH secretion is not well understood since PGE2 shows an inhibitory effect on AVP-induced ACTH secretion.     

Selective inhibition of leukotriene C4 synthesis in human neutrophils by ethacrynic acid

Addition of glutathione S-transferase inhibitors, ethyacrynic acid (ET), caffeic acid (CA), and ferulic acid (FA) to human neutrophils led to inhibition of leukotriene C4 (LTC4) synthesis induced by calcium ionophore A23187. ET is the most specific of these inhibitors for it had little effect on LTB4, PGE2 and 5-HETE synthesis. The inhibition of LTC4 was irreversible and time dependent. ET also had little effect on 3H-AA release from A23187-stimulated neutrophils.     

Antiabortifacient action of dibenzyloxyindanpropionic acid in mice

To evaluate the details of the adrenergic stimulation of urinary prostaglandins in man, ten normal volunteers were given various agonists and antagonists. The effect of 4 hour IV infusions of norepinephrine (NE), NE + phentolamine (PHT), NE + phenoxybenzamine (PHB), NE + prazosin (PZ), isoproterenol (ISO), and PHT alone on urinary PGE2 and PGI2 (6 keto PGF1 alpha) were determined. PGE2 and 6 keto PGF1 alpha were measured by radioimmunoassay from 4 hour urine samples. NE stimulated both PGE2 (196 +/- 40 to 370 +/- 84 ng/4 hrs/g creatinine and 6 keto PGF1 alpha (184 +/- 30 to 326 +/- 36), both p less than 0.01. In contrast, ISO had no effect on either PGE2 or 6 keto PGF1 alpha excretion. Alpha blockade with PHT. PHB, or PZ inhibited the NE induced systemic pressor effect. However, the effect of the alpha blockers on the NE induced stimulation of PGE2 and 6 keto PGF1 alpha varied. PHT did not alter the NE stimulated PGE2 or 6 keto PGF1 alpha release (370 +/- 84 vs. 381 +/- 80) PGE2 and (326 +/- 50 vs. 315 +/- 40) 6 keto PGF1 alpha both p greater than 0.2). PHT alone stimulated only 6 keto PGF1 alpha. PHB and the specific alpha 1 antagonist PZ similarly eliminated the NE induced prostaglandin release. These results suggest that adrenergically mediated urinary prostaglandin release in man is via an alpha receptor with alpha 1 characteristics.     

Endothelin-1 in hypertension in the baroreflex-intact SHR: a role independent from vasopressin release

This study sought to identify whether central endothelin (ET) receptor activation contributes to the elevated pressure in spontaneously hypertensive rats (SHR) and whether an ET-stimulated vasopressin (AVP) release mediates the increased pressure. In Wistar Kyoto (WKY) rats, intracerebroventricular ET-1 induced a dose-dependent pressor response that was shifted rightward in SHR. ET(A) antagonism decreased mean arterial pressure in baroreflex-intact SHR (P<0.01), consistent with inhibition of endogenous ET-1, and blocked the pressor response to exogenous ET-1 in both strains. ET-1 increased AVP only after sinoaortic denervation (P<0.05). Contrary to WKY, sinoaortic denervation was required to elicit a significant pressor response with 5 pmol ET-1 in SHR. Sinoaortic denervation permitted ET-1 to increase AVP in both strains, and peripheral V(1) blockade decreased pressure in denervated but not intact rats. After nitroprusside normalized pressure in SHR, the pressor and AVP secretory responses paralleled those in WKY. Thus endogenous ET(A) receptor mechanisms contribute to hypertension, independent of AVP, in baroreflex-intact SHR. Although blunted in the hypertensive state, the arterial baroreflex buffers the ET-1-induced pressor and AVP secretory responses in both strains.     

Development of prejunctional alpha 2 adrenergic receptor mediated feedback control of the pressor response to sympathetic nerve stimulation in hypertensive and normotensive rats

Development of prejunctional alpha 2 adrenergic receptor inhibition of pressor responses to sympathetic nerve stimulation in the spontaneously hypertensive Wistar-Kyoto rat was compared with genetically similar (Wistar-Kyoto) and different (Sprague-Dawley) normotensive rats. The sympathetic outflow was stimulated at frequencies of 1 to 20 Hz in pithed rats at 10,14,20 and 60 days of age. The antagonist, rauwolscine was given to block alpha 2 mediated feedback inhibition of noradrenaline release and the incidence of enhanced pressor responses determined. In Sprague-Dawley but not in spontaneously hypertensive or Wistar-Kyoto rats the changes in the incidence of enhanced responses parallel development of indices of sympathetic activity in other studies of the rat. Thus at 10 days of age (when activity is low), the incidence of rauwolscine-enhanced responses was 45%; at 14 days, (coinciding with onset of baroreflex control), incidence fell to 14%; in the 3rd postnatal week (when there is sympathetic hyperactivity), incidence increased to greater than 90%; finally, incidence, like activity declined in adults. In Wistar-Kyoto rats, the incidence of enhanced responses was like the other strains at 10 days but then decreased during development. In spontaneously hypertensive rats, enhanced responses were also less evident during week 3 and greatly diminished in adults. We conclude that in the spontaneously hypertensive and normotensive variants of Wistar-Kyoto strain rats the limit of alpha 2 adrenergic receptor feedback control of noradrenaline release is reached prematurely and is attenuated relative to the level of neuronal activity. In keeping with this hypothesis, the basal rate of noradrenaline utilization (measured in kidney) was higher at 20 days in Wistar-Kyoto than in Sprague-Dawley, but Sprague-Dawley showed greater enhancement of noradrenaline level and utilization after rauwolscine. Thus, the limitation to feedback control may be in development of prejunctional alpha 2 adrenergic receptors and/or their coupling to transmitter synthesis and release. Attenuated prejunctional alpha 2 adrenergic receptor inhibition is not linked obligatorily to development of hypertension in the spontaneously hypertensive Wistar-Kyoto rat.     

Downstream divergence of the ethylene signaling pathway for harpin-stimulated Arabidopsis growth and insect defense

Ethylene (ET) signal transduction may regulate plant growth and defense, depending on which components are recruited into the pathway in response to different stimuli. We report here that the ET pathway controls both insect resistance (IR) and plant growth enhancement (PGE) in Arabidopsis (Arabidopsis thaliana) plants responding to harpin, a protein produced by a plant pathogenic bacterium. PGE may result from spraying plant tops with harpin or by soaking seeds in harpin solution; the latter especially enhances root growth. Plants treated similarly develop resistance to the green peach aphid (Myzus persicae). The salicylic acid pathway, although activated by harpin, does not lead to PGE and IR. By contrast, PGE and IR are induced in both wild-type plants and genotypes that have defects in salicylic acid signaling. In response to harpin, levels of jasmonic acid (JA) decrease, and the COI1 gene, which is indispensable for JA signal transduction, is not expressed in wild-type plants. However, PGE and IR are stimulated in the JA-resistant mutant jar1-1. In the wild type, PGE and IR develop coincidently with increases in ET levels and the expression of several genes essential for ET signaling. The ET receptor gene ETR1 is required because both phenotypes are arrested in the etr1-1 mutant. Consistently, inhibition of ET perception nullifies the induction of both PGE and IR. The signal transducer EIN2 is required for IR, and EIN5 is required for PGE because IR and PGE are impaired correspondingly in the ein2-1 and ein5-1 mutants. Therefore, harpin activates ET signaling while conscribing EIN2 and EIN5 to confer IR and PGE, respectively.     

Methyl xanthine phosphodiesterase inhibitors behave as prostaglandin antagonists in a perfused rat mesenteric artery preparation.

The methyl xanthines, theophylline, caffeine and 3-isobutyl-1 methyl xanthine (MIX) inhibited the pressure responses to noradrnealine, angiotensin II and potassium ions in the isolated perfused mesenteric vascular bed of the male rat. The ID50s for inhibition of responses to noradrenaline were 1.85 mug/ml (0.83 x 10(-5) M) for MIX, 18 mug/ml (1 x 10(-4)M) for theophylline and 133 mug/ml (6.8 x 10(-4) M) for caffeine. Similar ID50 concentrations were found for responses to angiotensin II and potassium. We have previously found that substances which inhibit the three pressor agents equally may be prostaglandin (PG) synthesis inhibitors or PG antagonists. Xanthine itself, cyclic AMP and dibutyrl cyclic AMP had no inhibitory effects on the preparation up to concentrations of 10-2 M. Partial inhibition of PG synthesis by indomethacin shifted the % inhibition/log concentration curve to the left, while addition of exogenous PGE2 shifted it to the right. In preparations completely inhibited by sufficient indomethacin added to the perfusate to block PG synthesis, and then restored by adding 1 or 5 ng/ml PGE2 in addition to the indomethacin, the methyl xanthines again inhibited responses suggesting that they were PG antagonists rather than inhibitors of synthesis or release. In preliminary experiments MIX also inhibited effects of PGF2alpha on rat uterus and PGE1 on guinea pig ileum. Effective concentrations of theophylline were similar to the therapeutic levels in human plasma. PG antagonists may be a major action of methyl xanthines requiring reinterpretation of many experiments which have attributed their effects to PDE inhibition. PGs may also be involved in regulating PDE action.     

Effects of endogenous and exogenous prostaglandin in neurotransmission in canine trachea

The effect of PGE2 on neurotransmission in the canine tracheal strip dissected free of epithelium was studied in the single sucrose gap and organ bath. PGE2 was a potent inhibitor of the initiation of excitatory junction potentials (ejps) by just submaximal nerve stimulation. In a concentration of 10(-9) or 10(-8) M PGE2 nearly or completely abolished them. Contractile responses to field stimulation in the sucrose gap at 27 degrees C or in muscle baths at 37 degrees C were also reduced or abolished by PGE2 in the same dose range; reductions were greater at low frequency. Responses to acetylcholine were also depressed but significantly less than to field stimulation. These are consistent with major presynaptic as well as some postsynaptic inhibitory actions of PGE2. No evidence was obtained that endogenous PGE2 affected excitatory junction potentials and contractions; i.e. they were stable for hours and unaffected by indomethacin 10(-6) and 10(-5) M under our conditions. Post-stimulus potentiation of ejps amplitude, maximum at 10 s, was observed and became more marked after the first ejp had been markedly reduced or abolished by PGE2. This potentiation was unaffected by indomethacin. It was suggested that a presynaptic process inhibited by PGE2 might participate in this potentiation. The canine trachea is a useful preparation when studied under the experimental condition used here for study of effects of products of arachidonate on neurotransmission.     

An Ex Vivo Method for Evaluating Prostaglandin Synthetase Activity in Cortical Slices of Mouse Brain

The release of prostaglandin E2 (PGE2) from cortical slices of mice into incubation medium is followed for 3 h and compared to PGE2 levels in the corresponding slice. Immediately after decapitation, the rate of PGE2 released into the incubation medium is elevated and a steady low rate of spontaneous release is gained within 1-2 h of incubation. PGE2 synthesis and release is blocked in a dose-dependent manner by either indomethacin (3 X 10(-6) -3 X 10(-4) M) or flufenamic acid (2.6 X 10(-6) M) either when added in vitro or administered in vivo. Full recovery of PGE2 synthesis is reached after 3 h incubation of slices following in vivo administration of indomethacin. In vivo administration of flufenamic acid results in prolonged inhibition of PGE2 released in vitro. The inhibition of PGE2 released by indomethacin is also correlated with the slice PGE2 content. Administration of lipopolysaccharide (LPS), a known activator of phospholipase A2, results in a fivefold increase in PGE2 and a twofold increase in 6-keto-PGF1 alpha released into the medium. The release of thromboxane B2 is not affected by LPS.     

Nitric oxide modulation of ET(B) receptor-induced vasopressin release by rat and mouse hypothalamo-neurohypophyseal explants

Endothelin (ET) peptides stimulate vasopressin (AVP) secretion via ET(B) receptors at hypothalamic loci. Nitric oxide modulates the actions of ET in the cardiovascular system and also influences neurotransmission and specifically suppresses firing of magnocellular neurons. The purpose of these studies was to ascertain whether nitric oxide, generated in response to ET(B) receptor stimulation, buffers the stimulatory effect of ET and suppresses AVP release. Studies were performed using a pharmacological approach in hypothalamo-neurohypophyseal explants from rats, and an alternative strategy using explants from mice with an inactivating mutation of neuronal NOS (nNOS-/-) and their wild-type parent strain. Whole explants in standard culture or only the hypothalamus of compartmentalized explants was exposed to the ET(B) selective agonist, IRL 1620 (10(-13) to 10(-8) M). Rat and wild-type mouse explants displayed similar responses, although absolute basal release rates were higher from murine explants. Maximal AVP release at 0.1 nM IRL 1620 was 311 +/- 63 (rat) and 422 +/- 112% basal x explant(-1) x h(-1) (mouse). Sodium nitroprusside (SNP; 0.1 mM) suppressed maximal AVP release to basal values. N(omega)-nitro-L-arginine methyl ester (L-NAME, 0.1 microM), which did not itself stimulate AVP secretion, more than doubled the response to 1 pM IRL 1620, from 136 +/- 28 to 295 +/- 49% basal x explant(-1) x h(-1) (P < 0.05) by rat explants. Explants from wild-type mice responded similarly. Explants from nNOS-/- mice had higher basal AVP secretory rate in response to 1 pM IRL 1620: 271 +/- 48 compared with 150 +/- 24% basal x explant(-1) x h(-1) (P < 0.05) from wild-type murine explants. In the nNOS-/-, SNP suppressed stimulated release, and L-NAME exerted no additional stimulatory effect: 243 +/- 38% basal x explant(-1) x h(-1). Thus nitric oxide inhibits the AVP secretory response induced by ET(B) receptor activation within the hypothalamo-neurohypophyseal system and is generated primarily by the nNOS isoform. The modulation of AVP secretion by ET and also nitric oxide can take place independently from their effects on cerebral blood flow, systemic hemodynamics, or the arterial baroreflex.     

The possible involvement of cytochrome P-450 monooxygenase in AVP-induced ACTH secretion

AVP (10(-7) M) induced ACTH as well as PGE2 release from rat anterior pituitary quarters. Inhibitors of P-450 monooxygenase, metyrapone (10 mM) and piperonyl butoxide (1 mM and 10 mM) attenuated the ACTH and PGE2 response to AVP. 7,8-benzoflavon (10 mM) which inhibits 3-methylchloranthrene inducible form of P-450 isoenzymes showed no inhibition of AVP-induced ACTH secretion. The decrease in ACTH response to AVP was still observed following the inhibition of prostaglandin synthesis by indomethacin. These results suggest that cytochrome P-450 monoocygenase systems are involved in the process of AVP-induced ACTH secretion, 3-methylchloranthrene inducible form of P-450 isoenzymes do not seem to be involved in this process.     

Effect of synthetic cyclic nucleotides on immunologic histamine release from calf granulocytes.

Sensitized bovine granulocytes release histamine when exposed to specific antigens. A unique modulation of histamine release by adrenergic agents has been shown in the bovine; beta-adrenergic agonists enhance and alpha-adrenergic agonists inhibit histamine release. This is an opposite response to that reported in other species. The present study was undertaken to determine the possible relationship between cyclic nucleotides and adrenergic agents in this species. Dibutyryl cAMP enhanced antigen-induced histamine release over the complete concentration range tested (10(-6)--10(-3)M); it also overcame, in a dose-dependent manner, the inhibition of antigen-induced histamine release produced by 10(-4) M phenylephrine. The 8-bromo cGMP AND 0-MONOBUTYRYL CGMP had no significant effect on antigen-induced histamine release nor did 8-bromo-cGMP have any significant effect on the enhancement of histamine release produced by 10(-4) M dibutyryl cAMP. These findings suggest that only cAMP has a role in the modulation of antigen-induced histamine release from bovine granulocytes.     

Glycine blocks the increase in intracellular free Ca2+ due to vasoactive mediators in hepatic parenchymal cells

Recently, glycine has been shown to prevent liver injury after endotoxin treatment in vivo. We demonstrated that ethanol and endotoxin stimulated Kupffer cells to release PGE(2), which elevated oxygen consumption in parenchymal cells. Because glycine has been reported to protect renal tubular cells, isolated hepatocytes, and perfused livers against hypoxic injury, the purpose of this study was to determine whether glycine prevents increases in intracellular free Ca(2+) concentration ([Ca(2+)](i)) in hepatic parenchymal cells by agonists released during stress, such as with PGE(2) and adrenergic hormones. Liver parenchymal cells isolated from female Sprague-Dawley rats were cultured for 4 h in DMEM/F12 medium, and [Ca(2+)](i) in individual cells was assessed fluorometrically using the fluorescent calcium indicator fura 2. PGE(2) caused a dose-dependent increase in [Ca(2+)](i) from basal values of 130 +/- 10 to maximal levels of 434 +/- 55 nM. EGTA partially prevented this increase, indicating that either extracellular calcium or agonist binding is Ca(2+) dependent. 8-(Diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), an agent that prevents the release of Ca(2+) from intracellular stores, also partially blocked the increase in [Ca(2+)](i) caused by PGE(2), suggesting that intracellular Ca(2+) pools are involved. Together, these results are consistent with the hypothesis that both the intracellular and extracellular Ca(2+) pools are involved in the increase in [Ca(2+)](i) caused by PGE(2). Interestingly, glycine, which activates anion (i.e., chloride) channels, blocked the increase in [Ca(2+)](i) due to PGE(2) in a dose-dependent manner. Low-dose strychnine, an antagonist of glycine-gated chloride channel in the central nervous system, partially reversed the inhibition by glycine. When extracellular Cl(-) was omitted, glycine was much less effective in preventing the increase in [Ca(2+)](i) due to PGE(2). Phenylephrine, an alpha(1)-type adrenergic receptor agonist, also increased [Ca(2+)](i), as expected, from 159 +/- 20 to 432 +/- 43 nM. Glycine also blocked the increase in [Ca(2+)](i) due to phenylephrine, and the effect was also reversed by low-dose strychnine. Together, these data indicate that glycine rapidly blocks the increase in [Ca(2+)](i) in hepatic parenchymal cells due to agonists released during stress, most likely by actions on a glycine-sensitive anion channel and that this may be a major aspect of glycine-induced hepatoprotection.     

Effect of endothelin-1 on release of arginine-vasopressin from perifused rat hypothalamus

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide with potent pressor activity. We studied the effect of ET-1 on release of arginine-vasopressin (AVP) from perifused rat hypothalamus. ET-1 (10(-10) to 10(-8) M) significantly stimulated AVP release. The ET-1-induced AVP release was completely blocked in the presence of nicardipine. Our results suggest a possible involvement of ET in the regulation of AVP release.