Effect of oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin in the rat.

The effect of three oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin was investigated in conscious male rats infused with hypotonic saline. Infusion of oxytocin at 100 pg/min produced plasma concentrations of 12.7 +/- 3.3 pmol/l and led to significant increases in sodium excretion, urine flow and glomerular filtration rate (GFR). The increase in sodium excretion of 42 +/- 9% during oxytocin infusion was significantly decreased by all three antagonists to 15 +/- 5% (10 ng [mercapto-proprionic acid1, D-Tyr(Et)2,Thr4,Orn8]-oxytocin/min), 13 +/- 5% (5 ng desGly9[D-Trp2,Thr4,Orn8]-dC6oxytocin/min) and 4 +/- 5% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/min). Similarly, the increase in urine production of 22 +/- 5% associated with oxytocin infusion was significantly decreased to 4 +/- 3% (5 ng desGly9[D-Trp2,D-Thr4,Orn8]-dC6 oxytocin/min) and 1 +/- 4% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/ min). All three antagonists blocked the oxytocin-induced increase in GFR when infused at 10 ng/min. Infusion of vasopressin at 160 pg/min produced plasma concentrations of 10.1 +/- 2.1 pmol/l and this led to a significant increase in sodium excretion and a significant decrease in urine flow rate. None of the antagonists had any effect on the natriuretic or antidiuretic actions of vasopressin suggesting that different receptors are involved in these renal actions of the two peptides.

Do vasopressin and oxytocin have synergistic renal effects in the conscious rat?

The renal effects of arginine vasopressin and oxytocin were studied in the conscious unrestrained rat infused with 0.077 M NaCl. Peptides were infused at rates of 24 and 160 pmol/min (vasopressin) or 30 and 200 pmol/min (oxytocin) either alone or as a combination of the two lower or two higher doses. The rates of infusion were selected to give ratios of oxytocin:vasopressin similar to those seen in the plasma of euhydrated and dehydrated rats. Vasopressin produced dose-dependent antidiuretic and natriuretic responses, the natriuresis commencing after 15-30 min infusion. Oxytocin produced dose-dependent diuretic and natriuretic responses, the natriuresis commencing within the first 15 min of infusion. Combined infusion of vasopressin and oxytocin produced dose-dependent antidiuretic responses which were comparable to those seen with vasopressin alone. The natriuretic response from combined infusion at the higher rate appeared to have the greater magnitude for individual 15-min periods of the vasopressin response combined with the longer duration of the oxytocin response. Although the total natriuretic response was therefore greater, this difference failed to reach significance. Only the higher rates of infusion of vasopressin and oxytocin significantly increased the clearance of sodium, by 53 +/- 23 and 62 +/- 18% and glomerular filtration rate (GFR) by 23 +/- 4 and 23 +/- 4% respectively. The clearance of sodium during the combined hormone infusion was significantly greater (109 +/- 21%), while the rise in GFR at 23 +/- 5% was comparable to that seen when each hormone was given separately.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of vasopressin and oxytocin on glomerular filtration rate in the conscious rat: contribution to the natriuretic response.

Urine flow, sodium excretion, mean arterial blood pressure and glomerular filtration rate (GFR) were determined in the conscious unrestrained rat infused with hypotonic saline. The effects of vasopressin infused at 24 and 160 pmol/min and oxytocin infused at 30 and 200 pmol/min were determined. The lower doses of each hormone gave plasma concentrations within the physiological range whereas the higher doses produced plasma concentrations equivalent to those seen following dehydration. Vasopressin produced dose-dependent antidiuretic and natriuretic responses. Hormone infused at both rates increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. Fractional excretion of sodium was significantly elevated by both doses. Oxytocin produced dose-dependent diuretic and natriuretic responses. Again both rates of infusion increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. The lower dose caused a significant increase in the fractional excretion of sodium. It appears, therefore, that increases in GFR may have a role in the natriuretic response to both hormones. However, this response can also be seen when GFR remains unchanged. This fact, together with the observed increases in the fractional excretion of sodium, indicates that these hormones have additional tubular actions.