Hypotensive effect of intravenous injection of tachykinins in conscious, freely moving spontaneously hypertensive and Wistar Kyoto rats.
The present study evaluated the sensitivity of spontaneously hypertensive (SHR) and of Wistar Kyoto (WKY) rats to the hypotensive effect of tachykinins (TKs). Eledoisin, substance P, and the NK-1-selective agonist [Sar9,Met(O2)11]substance P evoked a smaller hypotensive response in SHR than in WKY rats. The hypotensive effect of NKA was slightly smaller in SHR, but no significant strain difference was observed. The NK-2-selective agonist [beta Ala8]NKA(4-10) was a very weak hypotensive agent in WKY rats, while being completely inactive in SHR. The NK-3-selective agonists [Asp5,6,MePhe8]substance P(5-11) and [MePhe7]NKB did not modify blood pressure in both strains. Heart rate was essentially unmodified following the NK-3 agonists, while it was increased after injection of substance P, [Sar9,Met(O2)11]substance P, and neurokinin A, the increase being greater in WKY than in SHR. Surprisingly, eledoisin increased heart rate in SHR, but not in WKY rats, despite the greater hypotensive effect elicited in the latter strain. The present results confirm that the hypotensive effect of peripheral TKs is mediated by NK-1 receptors and show that SHR are less sensitive than WKY rats to this effect.
Pompei
P
P
Institute of Pharmacology, University of Camerino, Italy.
Tayebati
S J
SJ
Polidori
C
C
Perfumi
M
M
De Caro
G
G
Massi
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004600:Eledoisin / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D007022:Hypotension / Q000139:chemically induced*; D007275:Injections, Intravenous; D008297:Male; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D015320:Tachykinins; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; D004600:Eledoisin; D015288:Neurokinin A