Renal effects of recombinant prolactin in anaesthetized rats

OBJECTIVE: To re-examine the controversial possibility that prolactin exerts renal effects, using recombinant mouse prolactin (rmP), in the presence and absence of circulating vasopressin. DESIGN: In experiment 1, the renal effects of rmP were examined in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) lacking circulating vasopressin and normal animals of the parent Long Evans (LE) strain. In experiment 2, salt and water excretion were studied in fluid-loaded normal Sprague-Dawley (SD) rats, some of which received rmP. METHODS: In experiment 1, BDI and LE rats maintained in fluid balance were infused i.v. with each of three concentrations of rmP (10, 20 and 40 microg/ml per h) or maintained on 150 mmol/l NaCl vehicle (controls). In experiment 2, the SD rats were infused with 75 mmol/l NaCl in order to induce a state of diuresis comparable to that of BDI rats, some of them then receiving the rmP i.v. RESULTS: A profound rmP-induced dose-dependent decrease in urine excretion (P<0.005) and a lesser decrease in sodium excretion in the BDI rats was in marked contrast with the small but significant increase in urine excretion in the LE rats compared with controls (P<0.025). The rmP-infused fluid-loaded SD rats also demonstrated a significant (P<0.05) dose-related antidiuresis compared with the control animals, in addition to a decrease in sodium excretion. CONCLUSIONS: These results show that prolactin has a profound antidiuretic effect in the absence of circulating vasopressin. In contrast, when vasopressin is present in the circulation rmP has a small, but opposite, diuretic effect. Thus the use of a recombinant prolactin has provided evidence for renal effects of this hormone which are modified in the presence of the circulating neurohypophysial hormone vasopressin.

Role of endogenous vasopressin in development of gastric ulcer induced by restraint and water immersion

To elucidate the role of arginine vasopressin (AVP) in the development of stress-induced gastric ulcer, the mucosal lesions after restraint and water immersion were examined in Brattleboro strain rats with hereditary hypothalamic diabetes insipidus (DI) and in Long-Evans rats (LE) used as controls. Restrained animals were immersed in water for 2 h, and the size of lesion was expressed as percentage of the lesion area to the total glandular mucosal area, which were defined as ulcer index (UI). In DI rats, UI was significantly higher than in control LE rats, despite the attenuated responses of plasma adrenocorticotropic hormone (ACTH) to stress. Although subcutaneous injection of selective antidiuretic analogue 1-desamino-8-D-AVP did not affect UI, intracerebroventricular (icv) administration of AVP reduced UI in DI rats, and icv administration of V1 antagonist [d(CH2)5Tyr(Me)]AVP elevated UI in LE rats. These results indicate that endogenous AVP plays a role in preventing the formation of gastric ulcers induced by stress via a central V1 receptor. Furthermore, we suggest that elevation of ACTH in plasma is not essential in the development of stress-induced gastric ulcer in rats.

Role of vasopressin in hypertension: studies using the Brattleboro rat

Plasma arginine vasopressin (AVP) levels were elevated in both one-kidney, one-clip [1K-1C) and two-kidney, one-clip (2K-1C) hypertensive Long-Evans rats. Homozygous Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI), which are completely devoid of vasopressin, were made hypertensive using the 1K-1C Goldblatt models for renal hypertension. The 2K-1C DI rats developed hypertension at the same rate and to the same degree as normal 2K-1C hypertensive Long-Evans rats. The development of hypertension in 1K-1C DI rats was similar to the normal 1K-1C hypertensive Long-Evans rats. However, the absolute levels of systolic blood pressure reached were significantly less in the vasopressin-deficient rats. Treatment with 1-desamino-8-D-arginine vasopressin (DDAVP), the synthetic analogue of arginine vasopressin that has high antidiuretic but low pressor potencies, was associated with restoration of water balance in the volume-depleted DI rats and also restored blood pressure to hypertensive levels equivalent to the 1K-1C Long-Evans rats. These studies suggest that vasopressin is not essential for the development of experimental renal hypertension in rats but may contribute to the absolute levels of systolic blood pressure reached through its properties as an antidiuretic hormone.