Pharmacological Characterization of the Pressor Response to Tachykinins in Isolated Perfused Rat Kidney

Document Type

Article

Publication Date

12-1-1993

Description

The pharmacological effects of substance P (SP), neurokinin A (NKA), an amino terminal fragment of SP and related tachykinin receptor agonists on renal resistance vessels were assessed in isolated rat kidney perfused at constant rate (3 ml min-1 g-1 of tissue) with a modified Krebs-Ringer bicarbonate buffer. At a basal perfusion pressure (PP) of 75 ± 6 mm Hg (n = 5), bolus injections of SP (1-33.3 nmol) had no significant vasoactive effect. After a sustained increase in base-line PP (134 ± 10 mm Hg) produced by 1 μM phenylephrine, SP evoked a dose-dependent increase in PP. The largest dose of SP increased PP by 60 ± 5 mm Hg. Physalaemin and kassinin had similar effects as SP but caused a smaller increase in PP at the largest dose. NKA was less potent than the other tachykinins. The vasoconstrictor response to SP was not blocked by 1 μM phentolamine when angiotensin II (0.22-0.26 μM) was used to increase basal tone (n = 5). Thus, the response to SP is not mediated by norepinephrine. The N-terminal SP fragment, SP(1- 7), had no effect on PP, which suggested that the pressor response to SP is C-terminal dependent and tachykinin receptor mediated. The selective NK-1 receptor agonist, [Sar9,Met(O2)11]SP, had no significant effect on PP. By contrast, the selective NK-2 and NK-3 receptor agonist, GR64349 and [MePhe7]NKB, produced concentration-dependent pressor responses and were more potent than SP (116 ± 8 and 134 ± 15 mm Hg increases in PP at 33.3 nmol, respectively). These results suggest that the vasoconstrictor effect of tachykinins in the isolated rat kidney is mediated by NK-2 and NK-3 receptors.

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