Renal effects of intracerebroventricularly injected tachykinins in the conscious saline-loaded rat: receptor characterization.

Abstract

1. The effects of intracerebroventricularly (i.c.v.) injected substance P (SP), neurokinin A (NKA) and [MePhe7]neurokinin B (NKB) were investigated on renal excretion of water, sodium and potassium in the conscious saline-loaded rat. The central effects of [MePhe7]NKB were characterized with selective tachykinin antagonists for NK1 (RP 67580), NK2 (SR 48968) and NK3 (R 820) receptors. 2. Whereas SP or NKA (65 or 650 pmol) failed to modify the renal responses, [MePhe7]NKB (65-6500 pmol) produced dose-dependent and long-lasting (30-45 min) decreases in renal excretion of water (maximal reduction at 65 pmol: from 66.14 +/- 7.62 to 21.07 +/- 3.79 microliters min-1), sodium (maximal reduction at 65 pmol: from 10.19 +/- 2.0 to 1.75 +/- 0.48 mumol min-1) and potassium (maximal reduction at 65 pmol: from 4.31 +/- 1.38 to 0.71 +/- 0.27 mumol min-1). While 650 pmol [MePhe7]NKB elevated urinary osmolality, neither 65 pmol nor 6.5 nmol [MePhe7]NKB altered this parameter. 3. Both the antidiuresis and antinatriuresis induced by [MePhe7]NKB (65 pmol) were significantly blocked by the prior i.c.v. injection of R 820 (1.3 nmol, 5 min earlier), although the potassium excretion was only partially reduced. However, R 820 did not affect the antidiuresis and antinatriuresis elicited by endothelin-1 (1 pmol, i.c.v.). On its own, R 820 decreased renal potassium excretion with no effect on urinary osmolality and renal excretion of water and sodium. The i.c.v. co-injection of RP 67580 and SR 48968 (6.5 nmol each, 5 min earlier) failed to modify the renal responses to [MePhe7]NKB in a similar study. 4. The central effects of [MePhe7]NKB (65 pmol) on renal excretion were blocked by the prior i.v. administration of a linear peptide vasopressin V2 receptor antagonist (50 micrograms kg-1, 5 min earlier). 5. These results suggest that the central NK3 receptor, probably located in the hypothalamus, is implicated in the renal control of water and electrolyte homeostasis through the release of vasopressin in the conscious saline-loaded rat.