Pharmacological characterization of the pressor response to tachykinins in isolated perfused rat kidney.
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 microM 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 microM phentolamine when angiotensin II (0.22-0.26 microM) 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 agonists, 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
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Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City.
Hoover
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D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010803:Physalaemin / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology
D010446:Peptide Fragments; D018039:Receptors, Tachykinin; D015320:Tachykinins; D010656:Phenylephrine; D010803:Physalaemin; D013373:Substance P; C036877:substance P (1-7); D015288:Neurokinin A; D009638:Norepinephrine; D014439:Tyramine; D010646:Phentolamine