Cholecystokinin octapeptide inhibits carotid sinus barorefiex in anesthetized rats

( views:70, downloads:0 )
Journal Title:
Volume 56, Issue 01, 2004
Key Word:
cholecystokinin octapeptide (CCK-8);proglumide;Bay K 8644;baroreflex;L-NAME;mean arterial pressure

Abstract: The purpose of this study was to determine the effect of cholecystokinin octapeptide (CCK-8) on carotid sinus baroreflex in 36 anesthetized male rats by isolated carotid sinus perfusion in vivo. The results obtained are as follows. (1) By perfusion with CCK-8 (0.1, 0.5, 1.0 μmol/L), the functional curve of baroreflex was shifted to the right and upward, with a decrease in peak slope (PS) (P<0.001) and a reflex decrease (RD) in mean arterial pressure, while the threshold pressure (TP) and saturation pressure (SP) were significantly increased. Among the functional parameters of carotid sinus baroreflex, the changes in RD, PS and TP were dose-dependent. (2) Pretreatment with proglumide (100 μmol/L), a nonselective CCK receptor antagonist,the inhibitory effect of CCK-8 (0.5 μmol/L) on the baroreflex was significantly attenuated. (3) Pretreatment with L-NAME (100μmol/L), an inhibitor of nitric oxide (NO) synthase, did not affect the inhibitory action of CCK-8 (0.5 μmol/L). (4) Preperfusion with Bay K 8644 (500 nmol/L), an agonist of calcium channel, could attenuate the effect of CCK-8 (0.5 μmol/L). It is suggested that the inhibitory action of CCK-8 on the baroreflex may be mediated by the activation of its receptors in the carotid sinus baroreceptor, leading to an inhibition of stretch-sensitive channels and a decrease in Ca2+ influx. However, NO released from the endothelium seems not to be involved in the mechanism of this effect.

  • [1]Crawley JN, Corwin RL. Biological actions of cholecystokinin. Peptide 1994;15:731-755.
  • [2]Wank SA, Pisegna JR, De Weerth A. Cholecystokinin receptor family. Molecular cloning structure and functional expression in rat, guinea pig and human. Ann NY Acad Sci 1994;731:49-66.
  • [3]Janssen PJ, Gardiner SM, Compton AM, Bennett T.Mechanisms contributing to the differential hemodynamic effects of bombesin and cholecyotokinin in concious Long Evans rats. Br J Pharmacol 1991; 102:123-134.
  • [4]Bachelard H, Gardiner SM, Kemp PA, Bennett T.Involvement of capsaicin-sensitive neurons in the haemodynamic effects of exogenous vasoactive peptides: Studies in conscious, adult Long Evans rats treated neonatally with capsaicin. Br J Pharmacol 1992;105:202-210.
  • [5]Bunting MW, Bert PM, Widdop RE. Effects of the CCKA receptor antagonists SR27897B and PD140548 on baroreflex. Function in conscious rats. Eur J Pharmacol 1997;337:35-39.
  • [6]Zhao XY (赵晓云), Ling YL, Meng AH, Shan BE, Zhang JL. Effects of cholecystokinin octapeptide on rat cardiac function and its receptor mechanism. Acta Physiol Sin (生理学报) 2002;54(3):239-243.
  • [7]Gaw AG, Hills DM, Spraggs CF. Characterization of the receptors and mechanisms involved in the cardiovascular action of CCK-8 in the pithed rat. Br J Pharmacol 1995;115:660-664.
  • [8]Marker JD, Roberts ML. Chronotropic actions of cholecystokinin octapeptide on the heart. Regul Pept 1988; 20:251-259.
  • [9]Kurosaea M, Iijima S, Funakoshi A, Kawanami T, Miyasaka K, Bucinskaite V, Lundeberg T. Cholecystokinin-8 (CCK-8)has no effect on heart rate in rats lacking CCK-A receptors.Peptide 2001 ;22:1279-1284.
  • [10]Pagani FD, Taveira da Silva AM, Hamosh P, Garvey TQ 3rd, Gillis RA. Respiratory and cardiovascular efforts of intraventricular cholecystokinin, Eur J Pharmacol 1982;78:129-132.
  • [11]Wu YM (武宇明), He RR. Bradykinin inhibits carotid sinus baroreflex in anesthetized rats. Acta Physiol Sin (生理学报) 1999;51(3):303~309 (Chinese, English abstract).
  • [12]Yi XL(易小林), Fan ZZ, He RR. An automatic system controlled by computer for carotid sinus perfusion. Chin J Appl Physiol (中国应用生理学杂志) 1993;9(2):156-159(Chinese, English abstract).
  • [13]Grigg P. Biophysical studies of mechanoreceptors. J Appl Physiol 1986;60:1107-1115.
  • [14]Sharma RV, Chapleau MW, Hajduczok G, Wachtel RE,Waite LJ, Bhalla RC, Abboud FM. Mechanical stimulation increases intracellular calcium in nodose sensory neurons. Neuroscience 1995;66(4):433.
  • [15]Mendelwitz D, Kunze D. Characterization of calcium currents in aortic baroreceptor neurons. J Neurophysiol 1992;68(4):509.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615