Search

The release of arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) and their involvement in renal water and electrolyte metabolism in primary aldosteronism in humans were studied. An oral acute water load (20 ml/kg body weight) was given to each of 12 patients before and after surgical removal of their aldosterone-producing adenoma(s). Plasma AVP and ANH were measured simultaneously, and renal water and electrolyte metabolism and tubular functions were determined. The same water load was given to seven normal subjects and the same parameters were determined. In the presence of mineralocorticoid excess before the operation, plasma AVP was relatively low compared with plasma osmolality (Posm), but was not suppressed in response to decreases in Posm after the water load. Baseline plasma ANH was high and increased further after the water load; urinary dilution and diuresis both remained normal. After the operation, baseline plasma AVP was normal and decreased in response to the decrease in Posm after the water load, with normal urinary dilution and diuresis. Baseline plasma ANH was normal, and did not increase after the water load. The ratio of urinary K and Na clearances and distal tubular reabsorption of Na increased before the operation. These results suggest that there are perturbations of AVP and ANH release in primary aldosteronism, despite the normal urinary dilution after a water load.

To assess whether atrial natriuretic peptide (ANP) plays a role in the natriuresis induced by interleukin 1 beta (IL-1 beta), the following experiments were carried out. Experiment (Ex) I: IL-1 beta (7.5 micrograms/kg BW) was given intravenously (i.v.) in conscious hydrated rats (n = 6). Plasma ANP, vasopressin (AVP) osmolality (Posm), Na and K, urine Na (UNa V) and K excretion (UK V), osmolality and flow (UF), and mean arterial blood pressure (MABP) and heart rate were simultaneously determined. In the control group (n = 6), the drug was omitted, and the same protocols were carried out. Ex II: Three mg/kg BW of the specific ANP antagonist, HS-142-1 (HS), was administered i.v. and then, IL-1 beta (7.5 micrograms/kg BW) was given i.v. (n = 6). In the HS alone group (n = 6), IL-1 beta was omitted. The experimental protocols were the same as those in Ex I. IL-1 beta increased significantly plasma ANP and AVP and UNa V, but not UF, accompanied by decreases in Posm and UKV and increases in MABP (ExI). HS inhibited the natriuresis mediated by IL-1 beta, despite increases in plasma ANP and had no influence on plasma AVP and MABP. In the control (ExI) and HS alone (ExII) groups, these parameters did not change, except for decreases in Posm in both groups and increased plasma ANP in the latter. These results suggest that plasma ANP may play an essential role in the IL-1 beta-mediated natriuresis.

To examine the role of vasopressin (AVP) receptors in the regulation of the hemodynamics and release of atrial natriuretic peptide (ANP), and the participation of renal nerve inputs in the osmotic AVP release, hypertonic saline (HS) was infused into conscious, bilaterally nephrectomized rats with non-peptide, selective antagonists for the V1-receptor or V2-receptor of AVP. In the control group, HS alone increased mean arterial pressure, plasma ANP and AVP, plasma volume and plasma osmolality, and decreased the heart rate. In the V1-receptor antagonist group, an increase in the mean arterial pressure and a decrease in heart rate were completely abolished and an increase in plasma ANP was attenuated. In the V2-receptor antagonist group, increases in mean arterial pressure and plasma ANP and a decrease in heart rate were attenuated. However, the ratio of the changes in heart rate to the changes in mean arterial pressure in the V2-receptor antagonist group is significantly higher than that in the control group. In both experimental groups, increases in plasma AVP, plasma volume and plasma osmolality were not different from those in the control group. These results suggest that a HS-induced increase in mean arterial pressure is mediated by the pressor effect of AVP, mainly through V1-receptors, and that the depressor effect of AVP through V2-receptors may not influence tonically HS-induced hypertension. Moreover, HS-induced increase in plasma ANP is mediated mainly by increases in plasma volume and blood pressure, but may not be affected by a direct action of AVP to the heart. Renal afferent nerve inputs may not have effects on the regulation of osmotic AVP release.

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.

To assess whether nitric oxide (NO) formed by IL-1 beta affects vasopressin (AVP) and atrial natriuretic hormone (ANH) release and the regulation of blood pressure and body temperature, intravenous infusion of either N omega-nitro-L-arginine methyl ester (L-NAME) alone (50 micrograms/kg.body weight.min for 135 min), human recombinant interleukin 1 beta (IL-1 beta) alone (750 ng/kg.body weight.min for 120 min), or L-NAME (50 micrograms/kg.body weight.min for 135 min) with IL-1 beta (750 ng/kg.body weight.min for 120 min), was performed following priming doses of L-NAME (2 mg/kg.body weight) and IL-1 beta (7.5 micrograms/kg.body weight) into conscious rats (n = 6 each). In the control group, saline alone was administered. Plasma AVP and ANH, mean arterial blood pressure (MABP), heart rate (HR) and rectal temperature (RT) were determined. In response to L-NAME, plasma AVP significantly increased, but plasma ANH did not change, despite increases in MABP and decreases in HR. In response to IL-1 beta, both plasma AVP and ANH increased with decreases in MABP and RT without any changes in HR. With L-NAME and IL-1 beta, both plasma AVP and ANH increased, and depressor response to IL-1 beta was partly attenuated by L-NAME, without any changes in RT. With saline alone, none of these parameters changed during the study. These results suggest that NO may directly affect the release of AVP and ANH and the regulation of body temperature and blood pressure, but NO formed by IL-1 beta may not have direct effects on the release of these hormones, and the regulation of blood pressure and temperature.

To assess how interleukins (IL) affect the release of vasopressin (AVP), atrial natriuretic hormone (ANH), and ACTH and the regulation of blood pressure (BP), heart rate (HR) and rectal temperature (RT), the 3 doses of 1.73 (low dose, LD), 8.63 (medium dose, MD), and 43.16 pmol/100 gBW (high dose, HD) of human recombinant IL-1 beta were intravenously (iv) administered in conscious rats, and plasma AVP, ANH, and ACTH, BP, HR and RT were determined simultaneously. In the control group (CON), the drug was omitted. Circulatory IL-1 beta levels were determined in each dose, and indomethacin (1 mg/rat, IM) was administered iv in the HD and CON groups. Plasma IL-1 beta increased transiently following IL-1 beta administration in each group. Plasma AVP, ANH, and ACTH increased in the LD, MD, and HD groups, respectively. Mean arterial BP (MABP) and RT increased in the LD group, but HR did not change. In the MD and HD groups, MABP decreased at 30 min followed by its increase at 120 min, but RT in both groups decreased. In the CON group, these parameters did not change. IM attenuated plasma AVP and ACTH responses to HD and also inhibited decreases in MABP and RT. These results suggest that IL-1 beta affects the release of AVP and ACTH, blood pressure and thermogenesis via prostaglandins (PGs), but ANH release related to IL-1 beta may not be mediated by PGs.

To assess whether atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) participate in impaired water excretion in patients with hypothyroid states (HS), an oral acute water loading (WL) test (20 ml/kg.BW/45 min) was performed before and after L-thyroxine (T4) treatment in 5 hypothyroid patients. Plasma ANP, AVP, osmolality (Posm), total protein and renal water excretion were simultaneously determined, and these data were compared to the data from five normal subjects (NS). The impaired water excretion rate in HS was entirely improved in the euthyroid states (ES) after T4 therapy for at least 7 months. Plasma ANP in HS was lower than that in NS (5.9 +/- 0.9 vs. 16.5 +/- 3.6 pmol/L, P < 0.05), but increased after T4 treatment (21.2 +/- 5.7 pmol/L, P < 0.05). Plasma AVP in HS (1.6 +/- 0.5 pmol/L) showed a tendency to be lower than those in ES and NS (2.9 +/- 0.4 and 2.9 +/- 0.7 pmol/L), but did not respond to a fall in Posm after WL, unlike ES and NS. Significant positive correlations were noticed between Posm and plasma AVP in ES and NS, but not in HS. These results suggest that not only the impaired release and/or metabolisms of AVP and ANP, but also derangement of renal water and electrolytes handling might induce attenuation of CH2O formation in hypothyroid states.

To assess whether increases in circulating atrial natriuretic hormone (ANH) in response to the plasma volume expansion, besides the volume receptor-mediated mechanisms, attenuate the arginine vasopressin (AVP) response to increased plasma osmolality and whether changes in plasma AVP and ANH affect renal solute excretion under hypertonic plasma volume expansion, hypertonic saline (0.95 mol/l saline) alone, hypertonic saline with 6% dextran (6D-HS) and hypertonic saline with 9% dextran (9D-HS) were administered into anesthetized dogs. In the control study, 0.15 mol/l NaCl alone was administered. Plasma AVP and ANH and cardiovascular and renal functions were determined. Hypertonic saline and 9D-HS also were administered into the vagotomized and sham operated dogs, and the same parameters were determined. Mean blood pressure and heart rate never changed in all the groups, but central venous pressure and plasma volume increased markedly in 6D-HS and 9D-HS groups. In the control and hypertonic saline groups, central venous pressure increased slightly but plasma volume never changed. Plasma AVP increased in the order of hypertonic saline, 6D-HS and 9D-HS, but plasma ANH increased in reverse order. Vagotomy restored the AVP response to 9D-HS to 75% of its response to hypertonic saline, with a marked rise in plasma ANH. Urine sodium and potassium excretion and urine flow increased in hypertonic saline, 6D-HS and 9D-HS groups, but these increases were comparable among the groups. In the control group, these parameters never changed. These results suggest that the volume receptor-mediated vagal neural and ANH responses to the plasma volume expansion may have an effect on the suppression of the AVP response to osmotic stimuli, and increased plasma ANH release never potentiated the natriuresis under the hypertonic plasma volume expansion.

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.