The Effects of Two Analogues of Arginine‐vasopressin (Ornithine‐vasopressin and Desamino‐d‐arginine‐vasopressin) on Kidney Function in Sheep

Abstract

The effects of intravenous infusion of ornithine-vasopressin (OVP) and desamino-D-argininevasopressin (dDAVP) were studied in normal and hydrated Merino sheep. In normal sheep, OVP resulted in a diuresis, increased urinary sodium and potassium excretion, and a fall in the plasma potassium concentration. Renal plasma flow remained constant but glomerular filtration rate and filtration fraction rose markedly. dDAVP in normal sheep was antidiuretic, but its only significant effect was a small decrease in plasma osmolality. In the hydrated sheep OVP was antidiuretic and resulted in increased urinary excretion of sodium and potassium, and a fall in the plasma potassium level. Renal plasma flow fell, but glomerular filtration and filtration fraction tended to rise. dDAVP in the hydrated sheep was also antidiuretic but urinary sodium and potassium excretion was reduced. Renal plasma flow and glomerular filtration fell, with a small decrease in filtration fraction.These results suggest that the diuretic effect in normal sheep and the electrolyte-excreting effects in both normal and hydrated sheep of OVP are related to the increase in glomerular filtration, which in turn is dependent on the vasopressor activity of the hormone. The increase in glomerular filtration caused by OVP is due to an increase in the filtration fraction of an unchanged renal plasma flow, which could be brought about by an increase in renal efferent arteriolar tone.The effects of hydration of the sheep were the conventional increased urine flow, decreased urine osmolality and decreased solute-free water reabsorption. Sodium and potassium excretion rose slightly and plasma osmolality fell. Renal plasma flow and glomerular filtration both increased with little change in filtration fraction. These effects could be brought about by suppression of endogenous vasopressin and a decrease in both afferent and efferent renal arteriolar tone.Arginine-vasopressin (AVP) frequently has a diuretic effect in normal nondiuresing sheep [Kinne, Macfarlane and Budtz-Olsen, 1961;Cross, Thornton and Tweddell, 1963;Ostwald, 1963;Gans, 1964]. It can also increase glomerular filtration rate (GFR) in such sheep, but not in hydrated sheep in which the GFR is already elevated due to hydration and in which AVP is invariably antidiuretic [Yesberg, Henderson and Budtz-Olsen, 1973]. This suggests that an increase in GFR may be the reason for the diuretic activity of the hormone. The nonpressor, but highly antidiuretic AVP analogue, desamino-D-arginine-vasopressin (dDAVP) does not increase GFR or urine flow in normal sheep [Yesberg, Henderson and Budtz-Olsen, 1976], indicating that it is the vaso-active part of the hormone molecule which brings about these changes.The increase in GFR could be due to an increase in renal plasma flow (RPF) or filtration fraction (FF). Ornithine-vasopressin (OVP) is an analogue of AVP with similar pressor and antidiuretic potency [Yesberg, Henderson and BudtzOlsen, 1974] and we decided to study the effects of OVP on these parameters in normal and hyd...

The Selective Vasopressin Type 1a Receptor Agonist Selepressin (FE 202158) Blocks Vascular Leak in Ovine Severe Sepsis*

“…infusion (1.13 pmol•kg −1 •min −1 , ~30 mcL/min), beginning 1 hour after pneumonia induction and maintained for the remainder of the 24-h study period in addition to the titrated infusion of selepressin that was started and continued as described above. This infusion rate of dDAVP was shown to be antidiuretic in hydrated sheep (39) and was kept constant to magnify any potential effect of V 2 R activation. The infusion was started 1 hour after pneumonia induction to allow for plasma dDAVP concentration to closely approach steady-state by the time MAP levels would decrease sufficiently for selepressin infusion to be started—dDAVP infusion requires 2 hours to reach steady-state plasma concentration in sheep compared to 30 minutes for AVP (40, 41).…”

Inhibition by Angiotensin II of Some Vasopressin Effects on Renal Function in Sheep

“…The effects of AVP infusion at 115 pmol (5 mU).min-l were in every way similar to those produced by the infusion of the pressor analogue, ornithine-vasopressin (OVP), at a dose rate of 13 3pmol (5mU).min-1 [Yesberg, Henderson and Budtz-Olsen, 1978], except that the marked increase in UNaV and fall in Posmol, which were statistically insignificant during OVP infusion, were highly significant during AVP infusion. Many of the effects of OVP on renal function in either hydrated or non-hydrated sheep were shown to be dependent on the pressor activity of the hormone molecule since they did not occur with the nonpressor analogue, desamino-D-arginine-vasopressin.…”

“…AVP can also raise glomerular filtration rate (GFR) in these sheep [Yesberg, Henderson and Budtz-Olsen, 1973], and experiments with analogues of AVP suggest that the diuretic and electrolyte-excreting effects are dependent on the vasopressor activity of the hormone molecule and that they occur as a result of an increase in filtration fraction from an unaltered renal plasma flow (RPF) [Yesberg, Henderson and Budtz-Olsen, 1978]. The increase in endogenous AVP in response to dehydration is nevertheless associated with a decrease in water and electrolyte output [Yesberg, Henderson and Budtz-Olsen, 1970] and a fall in GFR and RPF [McDonald and Macfarlane, 1958].…”

The Effect of Intravenous Hypertonic Saline Infusion on Renal Function and Vasopressin Excretion in Sheep

“…Scott and Morton [1976] showed that the same dose rate of hypertonic saline raised plasma AVP levels three or four times, and these were similar to PAVP levels resulting from an infusion of I1I5 pmol.min-'. We have shown that AVP at a dose rate of 46pmol.min-t [Yesberg et al, 1973] and 11 5 pmol.min-' [Yesberg, N.E., unpublished] and that ornithine-vasopressin at a dose rate of 13'3 pmol.min-' [Yesberg et al 1978] can increase GFR significantly, though RPF remains unchanged, resulting in a rise in FF. It is possible therefore that the increase in GFR in the present experiments was at least partly due to the increase in AVP levels.…”

“…We have shown that AVP can increase glomerular filtration rate (GFR) in such sheep [Yesberg, Henderson and Budtz-Olsen, 1973] and have suggested that this could at least partly account for the increased electrolyte excretion as well as the diuresis [Yesberg, 1974]. These effects on water and electrolyte excretion and GFR have also been observed with the pressor analogues of AVP, lysine-vasopressin and ornithine-vasopressin [Yesberg, 1974] but not with the non-pressor analogue, desamino-D-arginine-vasopressin [Yesberg, Henderson and Budtz-Olsen, 1978]. It might be argued that these observations are responses to pharmacological amounts of the hormone, but Scott and Morton [1976] showed that intravenous hypertonic saline loading caused the release of endogenous AVP which was associated with, and probably the cause of, an increased water and salt excretion, and that the plasma AVP levels achieved were similar to those produced by an exogenous AVP infusion rate of 11-5 pmol.…”