Cardiovascular responses to rat/mouse hemokinin-1, a mammalian tachykinin peptide: systemic study in anesthetized rats.
Rat/mouse hemokinin-1 is a mammalian tachykinin peptide whose biological functions have not been well characterized. In the present study, an attempt has been made to investigate the effect and mechanism of action of rat/mouse hemokinin-1 on systemic arterial pressure after intravenous (i.v.) injections in anesthetized rats by comparing it with that of substance P. Our data showed that injection of rat/mouse hemokinin-1 (0.1, 0.3, 1, 3 and 10 nmol/kg) lowered systemic arterial pressure dose-dependently. This effect was significantly blocked by pretreatment with SR140333 (a selective tachykinin NK1 receptor antagonist) and the NO synthase inhibitor L-NAME (Nomega-nitro-L-arginine methyl ester hydrochloride), respectively, but was not affected by bilateral vagotomy or the muscarinic receptor blocker atropine. Compared to rat/mouse hemokinin-1, a dose of 3 nmol/kg of substance P caused biphasic changes in systemic arterial pressure (depressor and pressor responses). The results suggest that the mechanism of the depressor response caused by substance P was similar to rat/mouse hemokinin-1 in that it was inhibited by SR140333 and L-NAME, respectively, but that there was a component of the cardiovascular change induced by rat/mouse hemokinin-1 (but not substance P) that was attenuated by SR48968 (a selective tachykinin NK2 receptor antagonist). The depressor response induced by rat/mouse hemokinin-1 (i.v.) might be explained primarily by the action on endothelial tachykinin NK1 receptors to release endothelium-derived relaxing factor (NO) and this effect was not affected by vagal components. In addition, rat/mouse hemokinin-1 could not induce the pressor response through stimulation of sympathetic ganglion like substance P in anesthetized rats.
Fu
Cai-Yun
CY
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Biochemistry and Molecular Biology, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
Kong
Zi-Qing
ZQ
Long
Yuan
Y
Chen
Qiang
Q
Wang
Rui
R
D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology* / Q000502:physiology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology* / Q000502:physiology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology
D001549:Benzamides; D018727:Muscarinic Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011498:Protein Precursors; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; C423233:Tac4 protein, mouse; D015320:Tachykinins; C507968:hemokinin-1; C085215:SR 140333; D013373:Substance P; C073839:SR 48968; D001285:Atropine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester