To assess whether arginine vasopressin and atrial natriuretic hormone participate in impaired urinary dilution and excretion in glucocorticoid deficiency secondary to hypopituitarism. an acute oral water load of 20 ml·kg−1 BW was undertaken in the absence and presence of an oral hydrocortisone (60 mg) treatment in patients with ACTH deficiency (N= 7) and panhypopituitarism (N = 2). Plasma arginine vasopressin and atrial natriuretic hormone and renal water handling were simultaneously determined and compared with those in similarly water-loaded normal subjects. Plasma arginine vasopressin did not fall in response to decreased blood osmolality after an acute water load in the absence of hydrocortisone; plasma atrial natriuretic hormone did not change despite blood volume expansion; and impairment in urinary dilution and excretion remained. On the other hand, in the presence of hydrocortisone, plasma arginine vasopressin fell in response to a decrease in plasma osmolality and plasma atrial natriuretic hormone increased, thereby restoring urinary dilution and excretion. These results demonstrate that the impaired arginine vasopressin response to acute water loading play an essential role in deranged renal water and electrolyte handling in the state of glucocorticoid deficiency; the impaired release of atrial natriuretic hormone also may affect these disorders.
Tokihisa Kimura, Kozo Ota, Masaru Shoji, Minoru Inoue, Kazutoshi Sato, Masahiro Ohta, Tadasu Yamamoto, Yasuyuki Shimizu and Kaoru Yoshinaga
Kozo Ota, Tokihisa Kimura, Kuniaki Matsui, Kazuhiro Iitake, Masaru Shoji, Minoru Inoue, Kazutoshi Sato, Masahiro Ohta, Tadasu Yamamoto and Kaoru Yoshinaga
To assess the central effect of hypertonic NaCl on the release of vasopressin (AVP) and methionine enkephalin-like substances into the blood and cerebrospinal fluid, and on blood pressure, ventriculocisternal perfusion (0.25 ml/min, 60 min) was performed in anesthetized dogs with artificial cerebrospinal fluid (CSF), either isotonic (300 mosmol/kg) or hypertonic (600 and 1200 mosmol/kg). The effect of central administration of a V1-AVP antagonist on the central osmotic challenge was also studied. In dogs, given 600 mosmol/kg, CSF osmolality increased with a concomitant rise in mean arterial pressure and plasma AVP concentrations. Plasma osmolality, heart rate, CSF AVP and plasma and CSF methionine enkephalin-like substances showed no significant change. In dogs, given 1200 mosmol/kg, the CSF osmolality increase was accompanied by a rise in mean arterial pressure, heart rate, plasma AVP and CSF AVP. Plasma osmolality and plasma and CSF methionine-enkephalinlike substances did not change significantly. A V1-AVP antagonist given centrally attenuated the rise in mean arterial pressure induced by osmotic challenge. In dogs, given 300 mosmol/kg, no parameters changed significantly except for a gradual fall in heart rate. These results suggest that central osmotic stimulation by hypertonic NaCl increases blood pressure, heart rate and the release of AVP, but not methionine enkepholin-like substances, into the blood and CSF, and a V1-blocker given centrally attenuates the pressor response.
Kazutoshi Sato, Tokihisa Kimura, Kozo Ota, Masaru Shoji, Minoru Inoue, Masahiro Ohta, Tadasu Yamamoto, Takeharu Funyu, Kaoru Yoshinaga and Keishi Abe
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 NaCI 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.
Kozo Ota, Tokihisa Kimura, Minoru Inoue, Takeharu Funyu, Masaru Shoji, Kazutoshi Sato, Masahiro Ohta, Tadasu Yamamoto and Keishi Abe
Ota K, Kimura T, Inoue M, Funyu T, Shoji M, Sato K, Ohta M, Yamamoto T, Abe K, Effects of V1- and V2-vasopressin (AVP) antagonists on the pressor, AVP and atrial natriuretic peptide responses to a hypertonic saline infusion in conscious anephric rats. Eur J Endocrinol 1995;133:127–32. ISSN 0804–4643
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 nonpeptide, 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.
Kozo Ota, Second Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-77, Japan