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Renal effects of intrathecally injected tachykinins in the conscious saline‐loaded rat: receptor and mechanism of action
Author(s) -
Ding Yuan Yi,
Couture Réjean
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701223
Subject(s) - endocrinology , medicine , neurokinin a , neurokinin b , natriuresis , substance p , chemistry , denervation , renal function , saline , kidney , sodium , excretion , receptor , neuropeptide , organic chemistry
The effects of intrathecally (i.t.) injected substance P (SP), neurokinin A (NKA), [β‐Ala 8 ]NKA (4–10) and [MePhe 7 ]neurokinin B (NKB) at T 13 thoracic spinal cord level were investigated on renal excretion of water, sodium and potassium in the conscious saline‐loaded rat. Antagonists selective for NK 1 (RP 67580), NK 2 (SR 48968) and NK 3 (R 820; 3‐indolylcarbonyl‐Hyp‐Phg‐N(Me)‐Bzl) receptors were used to characterize the spinal effect of SP on renal function. Saline gavage (4.5% of the body weight) enhanced renal excretion of water, sodium and potassium over the subsequent hour of measurement. Whereas these renal responses were not affected by 0.65nmol SP, the dose of 6.5 nmol SP blocked the natriuretic response (aCSF value 3.9±0.8; SP value 0.7±0.3μmolmin −1 , P <0.01) as well as the renal excretion of water (aCSF value 48.9±5.8; SP value 14.5±4.0μlmin −1 , P <0.01) and potassium (aCSF value 4.8±0.6; SP value 1.5±0.6μmolmin −1 , P <0.01) at 30min post‐injection. SP had no significant effect on urinary osmolality. The SP‐induced renal inhibitory effects during the first 30min were abolished in rats subjected to bilateral renal denervation 1 week earlier or in rats injected i.t. 5min earlier with 6.5nmol RP 67580. In contrast, the co‐injection of SR 48968 and R 820 (6.5nmol each) did not affect the inhibitory responses to SP. On their own, these antagonists had no direct effect on renal excretion function. Since SP induced only transient changes in mean arterial blood pressure (−18.8±3.8mmHg at 1min and +6.3±2.4mmHg at 5min post‐injection), it is unlikely that the renal effects of SP are due to systemic haemodynamic changes. NKA (6.5nmol but not 0.65nmol) produced a transient drop in renal excretion of water (aCSF value 31.2±5.1; NKA value 11.3±4.2μlmin −1 , P <0.05), sodium (aCSF value 1.7±0.8; NKA value 0.4±0.2μmolmin −1 , P <0.05) and potassium (aCSF value 4.1±0.7; NKA value 1.5±0.4μmolmin −1 , P <0.05) at 15min post‐injection. However, the same doses (6.5nmol) of selective agonists for tachykinin NK 2 ([β‐Ala 8 ]NKA(4–10)) and NK 3 ([MePhe 7 ]NKB) receptors were devoid of renal effects. This study provided functional evidence that tachykinins may be involved in the renal control of water and electrolyte excretion at the level of the rat spinal cord through the activation of NK 1 receptors and the sympathetic renal nerve.