Masaru Shoji

Central Effects of Interleukin-1 on Blood Pressure, Thermogenesis, and the Release of Vasopressin, ACTH, and Atrial Natriuretic Peptide

To assess the central role of interleukin 1-beta (IL-1 beta) in the release of ACTH, vasopressin (AVP) and atrial natriuretic peptide (ANP) and in the regulation of blood pressure and thermogenesis, 3 ng (0.173 pM) x 100-1 x BW-1 (LIL), 30 ng (1.73 pM) x 100g-1 x BW-1 (MIL), and 150 ng (8.63 pM) x 100g-1 x BW-1 (HIL) of human IL-1 beta dissolved in sterile saline were injected intracerebroventricularly to conscious rats. In the control rats, saline alone (5 microliters) was administered. In three other groups, rats were pretreated with indomethacin, a cyclooxygenase inhibitor, given i.v. (1 mg x 100g-1 x BW-1); medium and high doses of IL-1 beta or its vehicle were given. In the LIL group, IL-1 beta increased blood pressure, body temperature and plasma AVP and ANP without any changes in heart rate (HR) and plasma ACTH. In the MIL group, plasma ACTH was increased, and changes in the other parameters were similar to those in the LIL group. In the HIL group, however, the pressor and thermogenetic responses were attenuated; plasma AVP, ACTH, and ANP were increased; and HR was unchanged. In the control (CON) group, none of these parameters was changed throughout the studies. Indomethacin abolished the AVP and ACTH responses to IL-1 beta, but potentiated the pressor and hypothermic responses and increased plasma ANP. These data suggest that the actions of IL-1 beta on AVP and ACTH release and thermogenesis, but not on blood pressure and the release of ANP, are modulated by the stimulated central production of prostaglandins.

Central effects of endothelin-1 on vasopressin and atrial natriuretic peptide release and cardiovascular and renal function in conscious rats

In order to investigate the central effect of endothelin-1 (ET-1) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular and renal function, either a high dose of ET-1 (3.5 ng/kg/min, HET-1) or a low dose (0.35 ng/kg/min, LET-1) was administered into the cerebral third ventricle in conscious rats. ET-1 increased the mean arterial blood pressure, but not heart rate, in a dose-related manner. LET-1 slightly stimulated AVP release, but not ANP release. HET-1 increased plasma AVP and ANP. Pretreatment with a V1-antagonist (TMeAVP) attenuated the blood pressure response to ET-1 and completely abolished increases in plasma ANP. Moreover, prazosin given i.v. completely prevented the residual pressure response. ET-1 did not significantly affect renal electrolytes and water handling. These results suggest that centrally administered ET-1 may increase the activity of the sympathetic nervous system and vasopressinergic neurons, resulting in an increase in blood pressure.

Effects of Acute Hypotensive Hemorrhage on Arginine Vasopressin Gene Transcription in the Rat Brain

To determine whether hypotensive hemorrhage has an effect on arginine vasopressin (AVP) gene expression, 16 ml/kg of arterial blood was drawn over 10 min in conscious unrestrained rats. Mean arterial blood pressure (MABP) and heart rate (HR) were measured, and the rats were decapitated before and 10 min, 1, 3, 6, 9, 12, and 24 h after the initiation of hemorrhage. The hypothalamic or cerebro-hypothalamic tissue was used to measure AVP mRNA by Northern blot analysis, and the trunk blood to measure plasma AVP, osmolality and hematocrit. Hemorrhage brought about rapid and transient decreases in MABP and HR accompanied by transient increases in plasma osmolality and AVP. Hematocrit decreased after the bleeding and reached a stable level 6 h after hemorrhage and thereafter. AVP mRNA was detected in the hypothalamus and not in the extrahypothalamic cerebral brain tissue under basal and posthemorrhage conditions. AVP mRNA in the cerebro-hypothalamic tissue increased by 1.8-fold at 6 h and 2.1-fold at 9 h after hemorrhage. These results indicate that AVP mRNA in the brain increases 6 h after increased AVP release in response to hypotensive hemorrhage.

The role of GABA in the central regulation of AVP and ANP release and blood pressure due to angiotensin and carbachol, and central GABA release due to blood pressure changes

To assess whether GABA given intracerebroventricularly (i.c.v.) affects vasopressin (AVP) and atrial natriuretic peptide (ANP) release and changes in blood pressure in response to i.c.v. angiotensin (AT II) and carbachol (CB), or whether changes in blood pressure affect GABA release in the brain, experiments were carried out. In experiment I (Ex I), GABA (100 micrograms) with AT II (50 ng) or CB (25 ng) was i.c.v. administered in conscious rats (n = 12). The same dose of AT II or CB alone also was administered without GABA (n = 12). In experiment II (Ex II), AT II (100 ng/kg per min) or nitropuruside (NP, 10 micrograms/kg per min) was intravenously (i.v.) infused and GABA release in the area adjacent to the paraventricular nucleus was determined, using the microdialysis method, in conscious rats (n = 12). In the experiments, mean arterial blood pressure (MABP), heart rate (HR), plasma AVP and/or ANP and plasma Na+ and K+ levels were measured. In Ex I, i.c.v. AT II increased plasma AVP and MABP without changes in HR and plasma ANP, but i.c.v. GABA never affected these responses. Icv CB also increased plasma AVP and MABP with decreased HR, but did not affect plasma ANP. Icv GABA abolished bradycardiac responses, but did not affect the others. In Ex II, the pressor response to i.v. AT II increased GABA release without apparent decreases in plasma AVP. However, the depressor response to NP produced decreases in GABA release with increased plasma AVP. These results shows that i.c.v. GABA did not affect AVP and pressor responses to i.c.v. AT II and CB, but changes in blood pressure modulates GABA release in the brain with changes in plasma AVP.

Role of intracerebral angiotensin receptors in the regulation of vasopressin release and the cardiovascular system.

In order to investigate the physiological role of the brain renin-angiotensin system in the regulation of vasopressin (ADH) release, angiotensin II (Ang II, 10 ng/kg/min) or 1-Sar-8-Ile-Ang II (50 ng/kg/min), an Ang II antagonist, was administered intracerebroventricularly to dogs (n = 42) anesthetized with urethane and chloralose after morphine sedation. The effects of the intravenous infusion of either 0.15 M or 2.5 M NaCl (0.1 ml/kg/min, 75 min) were also studied. In control dogs, artificial cerebrospinal fluid (ACSF) was administered at a rate of 10 microliter/min for 105 min. ACSF given intracerebroventricularly plus 0.15 M NaCl given intravenously did not affect ADH release, but 2.5 M NaCl given intravenously raised the plasma ADH level in parallel with the rise in plasma osmolality. Heart rate and blood pressure did not change significantly in ACSF along with 0.15 M NaCl, but heart rate increased significantly in ACSF along with 2.5 M NaCl. Ang II along with 0.15 M NaCl significantly raised plasma ADH and decreased heart rate without any changes in blood pressure. Ang II along with 2.5 M NaCl brought about a significant rise in plasma ADH level, arterial blood pressure, heart rate, and plasma osmolality. But simultaneous application of Ang II and 2.5 M NaCl did not result in a larger rise in plasma ADH than that expected from the effects of the two stimulations given separately. Namely, Ang II did not potentiate ADH release elicited by osmotic stimulation. Ang II antagonist given intracerebroventricularly neither affected ADH release and the cardiovascular system in 0.15 M NaCl nor inhibited ADH release in response to osmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of atrial natriuretic Peptide on the vasopressin response to osmotic and hemorrhagic stimuli in dogs.

Effect of atrial natriuretic peptide (ANP) on the vasopressin response to osmotic stimulation (Experiment I) as well as to hemorrhage (Experiment II) was investigated in anesthetized dogs. Moreover, cardiovascular function and renal water and electrolyte excretion were studied. In Experiment I, 2.5 M NaCI, containing 0.02 μg.kg 1 of ANP, was infused intravenously at a rate of 0.2 ml.kg−1, min 1 after one bolus injection of 0.75 μg.kg 1 ANP (HSA group). In the control group, 2.5 M NaCI alone (HS group) was infused. The infusion was continued for 75 min. In Experiment II, 0.15 M NaCI, containing the identical dose of ANP to Experiment I (HA group), or 0.15 M NaCI alone (H group) was infused intravenously during bleeding at a rate of 1 ml.kg−1.min −1 for 40 min. In Experiment I, infused ANP suppressed the vasopressin response to a mild osmotic stimulation, but not to a strong osmotic stimulation and attenuated ANP release and a rise in arterial and central venous pressures in response to plasma volume expansion, without the enhanced natriuresis. In Experiment II, infused ANP neither impaired the vasopressin response to bleeding nor potentiated a fall in mean arterial pressure and central venous pressure.

GENOTYPE ANALYSIS OF PREPRO-VASOPRESSIN SIGNAL PEPTIDE IN VASOPRESSIN-PRODUCING AND -NON-PRODUCING LUNG TUMORS

A polymorphism in the nucleic acid sequence encoding the signal peptide of the human prepro-vasopressin (AVP) has been reported in an AVP producing small cell lung carcinoma (SCLC) cell line. The difference predicts expression in tumor cells of a variant signal peptide with Pro for Leu 11. To clarify whether this difference is required for AVP secretion from SCLC cells and/or reflects increased mutagenesis in malignant tumors, the exon encoding the signal peptide of prepro-AVP in two AVP producing SCLC and 9 non-producing lung tumors was amplified using polymerase chain reaction. The variant sequence was neither found by direct sequencing nor by restriction enzyme analysis. These results suggest that similar to the hypothalamus the normal signal peptide is functional in tumor cells and that the variant signal peptide is not a prerequisite for AVP secretion from SCLC cells.

The roles of GABA in the central regulation of AVP and ANP release and blood pressure in hypertonic saline infusion and hemorrhage

In order to assess the central effects of gamma-aminobutyric acid (GABA) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular function, the following two experiments (Exp) were carried out in conscious rats (n = 24). Experiment I: GABA (10 micrograms/kg.min) was intracerebroventricularly (i.c.v.) administered into conscious rats receiving an intravenous (i.v.) infusion of 2.5 M NaCl, and the vehicle alone was i.c.v. administered under i.v. 2.5 M NaCl in the control group. Experiment II: GABA (12 micrograms/kg.min) was infused i.c.v. in conscious rats during hemorrhage (1.6% of BW) and the vehicle alone was i.c.v. administered during hemorrhage in the control study. In Experiment I, plasma AVP and ANP and mean arterial blood pressure (MABP) increased in response to 2.5 M NaCl, but heart rate (HR) slightly decreased. I.C.V. GABA attenuated the AVP and ANP responses, but did not affect MABP and HR. In Experiment II, plasma AVP increased due to decreases in MABP induced by hemorrhage, but plasma ANP and HR never changed. I.C.V. GABA did not affect plasma AVP and ANP, MABP and HR. These results show that i.c.v. GABA has an inhibitory effect on AVP and ANP release in response to hypertonic NaCl, but not to hemorrhage, but never affected hypertonic NaCl-induced increases in blood pressure.

Effects of endothelin-induced nitric oxide on venous circulation and renal water-electrolyte handling

To assess the interaction of endothelin (ET) with nitric oxide (NO) and the effects on venous circulation and handling of renal water and electrolytes, ET (1.0 ng/kg/min) or saline was administered with or without three doses (0.27, 2.7 and 27 ng/kg/min for 40 min) of N omega-nitro-L-arginine methyl ester (L-NAME), and NO synthase inhibitor, in anesthetized dogs. ET increased total peripheral resistance (TPR), pulmonary capillary wedge pressure (PCWP), urine flow (UF), and urinary K excretion (UKV), and decreased cardiac output (CO), urinary osmolality (Uosm), renal plasma flow (RPF), and glomerular filtration rate (GFR). L-NAME increased blood pressure (BP), TPR, PCWP, right atrial pressure (RAP), and mean circulatory filling pressure (MCFP), and decreased CO, RPF, and GFR, ET plus L-NAME markedly increased TPR, resistance to venous return, and plasma atrial natriuretic peptide (ANP), but not BP and MCFP, and curtailed the ET-induced responses in UF, UKV, and Uosm. Plasma aldosterone (ALD) was decreased in all groups, but plasma vasopressin (AVP) and renin activity (PRA) were not altered in any group. These results indicate that ET-induced NO formation might mitigate increases in venous as well as arterial vascular resistance and changes in renal handling of water and electrolytes, and might also play an inhibitory role in ANP release but not in PRA or AVP and ALD release.

Effects of Hemorrhagic Shock on Plasma Met-enkephalin, Vasopressin, Catecholamines, and Cardiovascular Functions in Intact and Adrenalectomized Dogs

It is well known that enkephalins in the brain, unlike the adrenal gland and sympathetic nervous system, coexist with vasopressinergic neurons in the hypothalamoneuro- hypophyseal system (Martin and Voigt 1981; Martin et al. 1983). Moreover, the enkephalin contents of this region have been reported to decrease in dehydrated rats and/or Brattleboro rats with a genetic defect in vasopressin synthesis (Marina et al. 1977; Rossier et al. 1979). Furthermore, it has recently been documented that plasma enkephalin-like immunoreactivity is increased in animals with endotoxic or hemorrhagic shock (Evans et al. 1984; Lang et al. 1982), reminiscent of vasopressin release in hypotensive shock (Share 1974).