EFFECT OF INTRARENALLY INFUSED PARATHYROID HORMONE-RELATED PROTEIN ONRENAL BLOOD-FLOW AND GLOMERULAR-FILTRATION RATE IN THE ANESTHETIZED RAT

1 Parathyroid hormone-related protein (PTHrP) is expressed in the kidn ey and acts on vascular PTH/PTHrP receptors to vasodilate the isolated kidney and to stimulate renin release. However, effects of PTHrP on r enal blood flow (RBF) and glomerular filtration rate (GFR) in vivo hav e not been assessed in the absence of its cardiac, peripheral and cent ral effects. We investigated the renal effects of PTH and PTHrP infuse d into the left renal artery of anaesthetized rats. 2 Intrarenal infus ions, adjusted to generate increasing concentrations of human PTHrP(1- 34) and rat PTH(1-34) in renal plasma (2 x 10(-11) to 6 x 10(-9) M) pr oduced a comparable dose-dependent increase in RBF. The rise was 4% at the lowest and 34% at the highest concentrations of peptides. Up to a concentration of 2 x 10(-9) M, mean arterial pressure (MAP) and heart rate were not affected, but at 6 x 10(-9) M, intrarenally infused pep tides reached the peripheral circulation, and caused a fall in MAP wit hin a few minutes. While MAP returned to basal value after the last pe ptide infusion, RBF remained more than 10% above control for at least 30 min. 3 Two competitive PTH/PTHrP receptor antagonists, [Nle(8,18), Tyr(34)]-bPTH(3-34) amide and [Leu(11), D-Trp(12)]-hPTHrP(7-34) amide (2 x 10(-8) M) were devoid of agonist activity, but markedly antagoniz ed the dose-dependent increase in RBF elicited by PTHrP. 4 GFR and uri ne flow were measured in left PTHrP-infused experimental kidney and ri ght control kidney. Renal PTHrP concentration of 10(-10) M elevated le ft PBF by 10%, and GFR by 20% without significantly increasing filtrat ion fraction, and increased urine flow by 57%. In the right control ki dney GFR and diuresis did not change. 5 The results indicate that PTHr P has similar renal haemodynamic effects as PTH and increases RBF, GFR and diuresis in anaesthetized rats.