RENAL EFFECTS OF INTRATHECALLY INJECTED TACHYKININS IN THE CONSCIOUS SALINE-LOADED RAT - RECEPTOR AND MECHANISM OF ACTION

1 The effects of intrathecally (i.t.) injected substance P (SP), neuro kinin A (NKA), [beta-Ala(8)]NKA (4-10) and [MePhe(7)]neurokinin B (NKB ) at T-13 thoracic spinal cord level were investigated on renal excret ion of water, sodium and potassium in the conscious saline-loaded rat. Antagonists selective for NK1 (RP 67580), NK2 (SR 48968) and NK3 (R 8 20; 3-indolylcarbonyl-Hyp-Phg-N(Me)-Bzl) receptors were used to charac terize the spinal effect of SP on renal function. 2 Saline gavage (4.5 % of the body weight) enhanced renal excretion of water, sodium and po tassium over the subsequent hour of measurement. Whereas these renal r esponses were not affected by 0.65 nmol SP, the dose of 6.5 nmol SP bl ocked the natriuretic response (aCSF value 3.9+/-0.8; SP value 0.7+/-0 .3 mu mol min(-1), P<0.01) as well as the renal excretion of water (aC SF value 48.9+/-5.8; SP value 14.5+/-4.0 mu l min(-1), P<0.01) and pot assium (aCSF value 4.8+/-0.6; SP value 1.5+/-0.6 mu mol min(-1), P<0.0 1) at 30 min post-injection. SP had no significant effect on urinary o smolality. The SP-induced renal inhibitory effects during the first 30 min were abolished in rats subjected to bilateral renal denervation 1 week earlier or in rats injected i.t. 5 min earlier with 6.5 nmol RP 67580. In contrast, the co-injection of SR 48968 and R 820 (6.5 nmol e ach) did not affect the inhibitory responses to SP. On their own, thes e antagonists had no direct effect on renal excretion function. Since SP induced only transient changes in mean arterial blood pressure (- 1 8.8+/-3.8 mmHg at 1 min and +6.3+/-2.4 mmHg at 5 min post-injection), it is unlikely that the renal effects of SP are due to systemic haemod ynamic changes. 3 NKA (6.5 nmol but not 0.65 nmol) produced a transien t drop in renal excretion of water (aCSF value 31.2+/-5.1; NKA value 1 1.3+/-4.2 mu l min(-1), P<0.05), sodium (aCSF value 1.7+/-0.8; NKA val ue 0.4+/-0.2 mu mol min(-1), P<0.05) and potassium (aCSF value 4.1+/-0 .7; NKA value 1.5+/-0.4 mu mol min(-1), P<0.05) at 15 min gest-injecti on. However, the same doses (6.5 nmol) of selective. agonists for tach ykinin NK2 ([beta-Ala(8)]NKA(4-10)) and NK3 ([MePhe(7)]NKB) receptors were devoid of renal effects. 4 This study provided functional evidenc e that tachykinins may be involved in the renal control of water and e lectrolyte excretion at the level of the rat spinal cord through the a ctivation of NK1 receptors and the sympathetic renal nerve.