VASCULAR EFFECTS OF PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PROTEIN IN THE SPLIT HYDRONEPHROTIC RAF KIDNEY

1. The effects of locally applied parathyroid hormone-related protein (PTHRP), a putative autocrine/paracrine hormone, on vascular diameters and glomerular blood flow (GBF) in the split hydronephrotic rat kidne y were studied. As PTHRP interacts with parathyroid hormone (PTH) rece ptors in all tissues tested so far, the effects of PTHRP were compared with those of PTH. 2. Preglomerular vessels dilated in a concentratio n- and time-dependent manner that was almost identical for PTH and PTH RP. A significant preglomerular vasodilatation (5-17%) occurred at a t hreshold concentration of 10(-10) mol l(-1) PTH or PTHRP, which raised GBF by 20 +/- 2 and 31 +/- 4%, respectively (means +/- S.E.M., n = 6) . PTH or PTHRP (10(-7) mol l(-1)) increased preglomerular diameters (1 1-36%) and GBF (60 +/- 10 and 70 +/- 8%, respectively) to near maximum . The most prominent dilatation was located at the interlobular artery and at the proximal afferent arteriole. 3. Efferent arterioles were n ot affected by either PTH or PTHRP. 4. Estimated concentrations of hal f-maximal response (EC(50)) for preglomerular vasodilatation and GBF i ncrease were in the nanomolar to subnanomolar range.5. After inhibitio n of angiotensin I-converting enzyme by 2 x 10(-6) mel kg(-1) quinapri l I.V. (n = 6), 10(-8) mol l(-1) PTHRP dilated preglomerular vessels a nd efferent arterioles (9 +/- 1% proximal and 6 +/- 1% distal). 6. We conclude that the renal vasculature of the hydronephrotic kidney is hi ghly sensitive to vasodilatation by PTH and PTHRP, which, in addition, may constrict efferent arterioles by Stimulating renin release. Thus, PTH and PTHRP could be potent modulators of renal haemodynamics and g lomerular filtration rate.