Effects of vasopressin-glycine and vasopressin-glycine-lysine-arginine on renal function in the rat

Abstract

ABSTRACT The peptides vasopressin-Gly and vasopressin-Gly-Lys-Arg occur as part of the sequence of the vasopressin-neurophysin precursor molecule and may be released from the hypothalamus and/or pituitary. [8-Lysine]-vasopressin-Gly (LVP-Gly) and [8-lysine]-vasopressin-Gly-Lys-Arg were administered i.v. to conscious, water-diuretic rats. The renal effects of the peptides were assessed by comparison with the actions of [8-lysine]-vasopressin (LVP) which was administered to separate groups of rats. LVP-Gly and LVP-Gly-Lys-Arg were weakly antidiuretic. LVP-Gly-Lys-Arg was the more potent of the two peptides, but on a molar basis it only had about 10% of the antidiuretic activity of LVP. LVP-Gly and LVP-Gly-Lys-Arg at 10 pmol/h per 100 g body weight (equivalent to the maximal antidiuretic dose of LVP) slightly decreased (P < 0·001) urine flow without causing significant changes in urine osmolality. LVP (10 pmol/h per 100 g body weight) promoted a marked natriuresis (P < 0·001 ) but LVP-Gly and LVP-Gly-Lys-Arg were not natriuretic, even at the dose which was markedly antidiuretic (100 pmol/h per 100 g body weight). Osmolal output decreased at all doses during administration of the extended peptides, but was not significantly changed in the control group or by LVP. Inulin clearance was decreased by about 30% during administration of both LVP and LVP-Gly-Lys-Arg at 100 pmol/h per 100 g body weight. It is concluded that LVP-Gly and LVP-Gly-Lys-Arg show weak antidiuretic activities and that the effect on urine flow may be partly due to a decrease in glomerular filtration rate (GFR). The decrease in osmolal output produced by the peptides is also a likely consequence of an effect on GFR. It is suggested that LVP-Gly and LVP-Gly-Lys-Arg have a low potential for activation of tubular vasopressin receptors, as shown by the weak antidiuretic activity and lack of a natriuretic action, but that they have a relatively stronger action on glomerular vasopressin receptors. J. Endocr. (1986) 108, 255–260