Siunmary. Urinary vasopre.ssin excretion rates in iumnal slieep liavf been .shown to range from less than I iiU/minute to 138 (lU/minute. They were inversely related to urine flow rate ancl directly related to urine osmolality. Deliydration led to an increase in Viisopressin excretion np to a rate of 869 {lU/niinnte which wii-s iLssodatetl with a decrease in urine flow rate ami an increase in o.sniohi]ity. Electrolyte excretion wa.s not siffnificantly related tn vasopressin excretion rate in either the normal or dehydrated jjroup, but both sodium and potassium ontiiut remained consi.stL'ntly low diiriu^ dehydration. Evidence is presented that increased vasopressin allow.s the reabsorption of more .solute-free water for a Kiven o.sm()lar clearance, and that where dehydration results in a retluction of sijhite-free water reabsorption it is due to a reduction in osmolar clearance, probably due to a vasopressin enhanced urea reabsorplion.

The effects of intravenous infusions of arginine vasopressin (AVP) alone and with angiotensin II (AII) on renal function were studied in conscious Merino ewes. AVP at 11-5 pmol.min-1 caused an increase in water and electrolyte output which was associated with a rise in glomerular filtration rate (GFR), solute clearance, solute-free water reabsorption and tubular sodium reabsorption. Addition of All of 100ng.mingenerally reversed all of these effects. The filtration fraction, which rose during AVP infusion, increased further when AII was added due to a greater fall in renal plasma flow than in GFR.The diuretic and electrolyte-excreting effects of infused AVP appear to be brought about by an increase in GFR. It is suggested that this inappropriate effect of AVP, which is secreted in response to water deprivation, could be countered by the simultaneous production of AII.Exogenous arginine-vasopressin (AVP) infused intravenously into non-hydrated or dehydrated sheep causes an increase in urine flow and electrolyte excretion [Kinne, Macfarlane and Budtz-Olsen, 1961; Cross, Thornton and Tweddell, 1963;Ostwald, 1963;Gans, 1964;Scott and Morton, 1976]. 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 diuretic and electrolyte-excreting effects of exogenous AVP have been observed with doses as low as 1 mU.min-1 in adult sheep [Cross and Thornton, 1966] and cannot be dismissed as merely pharmacological effects. Dehydration of sheep results in an increased output of renin [Blair-West, Brook and Simpson, 1972] as well as AVP, and it is possible that the subsequent increase in angiotensin II (All) might oppose the diuretic and electrolyte-excreting effects of AVP through its tendency to lower GFR and RPF [Navar and Langford, 1974]. The following experiments were undertaken as a preliminary investigation into the interaction between AVP and AII.161

SUMMARYSaralasin, an angiotensin II analogue and receptor blocker, was infused at 7 and 15 ,ug. min-' into dehydrated conscious Merino ewes. This caused mean arterial blood pressure, cardiac output, heart rate and renal vascular resistance to fall, and central venous pressure to rise. Renal plasma flow was unaffected but there were significant reductions in glomerular filtration rate, filtration fraction, urine flow, sodium and potassium excretion, solute clearance and solute-free water reabsorption. It is suggested that saralasin produced these effects by inhibiting endogenQus angiotensin II activity, and in particular by causing a reduction in renal post-glomerular resistance. This in turn caused a fall in glomerular filtration rate and filtration fraction. While saralasin might have had effects on renal tubular function and perhaps on vasopressin secretion, the observed effects on renal function can be explained by the decrease in glomerular filtration rate and filtration fraction.

Summary. Hydration of sheep lias been shown to result in a diuresis which is accompanied by a significant increase in glomerular filtration rate. Antidiuretic hormone has also been shown to cause an increase in glomerular filtration rate, observable only in those sheep where the initial glomerular filtration rate has not been raised by prior hydration.It is suggested that antidiuretic hormone has a two-fold effect on water excretion-an increase in water loss through its glomerular filtration rateaugmenting effect and a decrease in water loss tlirough its ability to increase tubular water reabsorption. The diuretic effect of antidiuretic hormone frequently observed in non-hydrated sheep, where glomerular filtration rate initially is low and tubular water reabsorption high, is probably due to a relatively large change in the former and a minor change in the latter of these two effects.

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...