C. Saussine et al., RENIN STIMULATING PROPERTIES OF PARATHYROID HORMONE-RELATED PEPTIDE IN THE ISOLATED-PERFUSED RAT-KIDNEY, Kidney international, 44(4), 1993, pp. 764-773
Previous studies showed that PTHrP exhibits renal vasodilating, arteri
olar cAMP stimulating and receptor binding properties. The present exp
eriments were designed to study whether PTHrP may influence renin secr
etion. Rat kidneys were isolated and single-pass perfused at constant
flow and stabilized pressure. Exposures to PTHrP or PTH stimulated a d
ose-dependent renin release reaching similar V(max). The affinity (0.1
nM) and threshold concentration (0.01 nm) for PTHrP were about 10 tim
es lower than for PTH. Compared to 10 muM isoproterenol, the maximum r
enin responses to PTHrP were similar but of shorter duration. The PTHr
P dose-response curve was not affected by 10 muM indomethacin. Adminis
tered simultaneously, PTHrP and PTH displayed no additive effects. PTH
rP-induced renin release as well as the role of extracellular calcium
were further studied in nonfiltering kidneys, which were perfused at a
constant flow and stable pressure in a closed circuit. Basal renin re
lease was inversely related with perfusate calcium and was depressed b
y the calcium ionophore BAY-K8644. PTHrP (100 nm) induced a 1.6-fold i
ncrease of basal renin release in normocalcic perfusate. Removing calc
ium abolished renin responses. PTHrP reversed the inhibiting effects o
f hypercalcic media or BAY-K8644 on basal renin release. The results s
upport calcium-mediated renin stimulating properties for PTHrP, via PT
H receptors, independently from baroreceptors, macula densa and prosta
glandins.