Published online Jun 14, 2005. doi: 10.3748/wjg.v11.i22.3405
Revised: March 21, 2004
Accepted: April 5, 2004
Published online: June 14, 2005
AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on cardiac functions and its receptor mechanism in endotoxic shock (ES) rats.
METHODS: The changes of the mean arterial pressure (MAP), heart rate (HR), the left ventricular pressure (LVP) and the maximal/minimum rate of LVP (±LVdp/dtmax)) were measured by using physiological record instrument in eight groups of rats. The expression of cholecystokinin-A receptor (CCK-AR) and cholecystokinin-B receptor (CCK-BR) mRNA of myocardium in ES rats was examined by reverse transcription polymerase chain reaction (RT-PCR).
RESULTS: (1) Low doses of sCCK-8 (0.4 μg/kg) caused tachycardia (441±27, normal control 391±22 s/min) and slight increase in MAP, LVP and ±LVdp/dtmax (16.96±1.79, 18.21±1.69 and +768.85±31.28/-565.04±27.71 kPa, respectively, all P<0.01), while medium doses (4.0 μg/kg) and high doses of sCCK-8 (40 μg/kg) elicited bradycardia and marked increase in MAP, LVP and ±LVdp/dtmax (17.29±1.63, 19.46±2.57 and +831.46±22.57/-606.08 ±31.32; 17.46±1.08, 19.83±2.91 and +914.52±35.95/-639.15±30.23 kPa, respectively, all P<0.01). Proglumide (1.0 mg/kg), a nonselective antagonist of CCK-receptor (CCK-R), significantly inhibited the pressor effects of sCCK-8 (15.96±1.38, 17.36±0.66 and +748.18±19.29/-512.12±14.39 kPa, respectively, all P<0.01), whilst reversing the bradycardiac responses. (2) High doses of LPS (8 mg/kg) elicited marked decrease in MAP, LVP and ±LVdp/dtmax. (7.16±0.59, 7.6±0.68 and +298.01±25.52/-166.96±19.25 kPa, respectively, all P<0.01). Pretreatment with sCCK-8 (40 μg/kg) could reverse the decline of cardiac functions (10.71±0.45, 11.7±1.26 and +446.04±67.18/-347.90±36.98 kPa, respectively, all P<0.01), while proglumide could cause further decline of cardiac function in ES rats (4.71±0.67, 5.58±1.25 and +226.48±15.84/-142.83±20.23 kPa, respectively, all P<0.01). (3) CCK-A/BR mRNAs were expressed in myocardium of control rats. Gene expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats. The increase of CCK-AR mRNA induced by LPS began at 0.5 h, peaked at 2 h, kept a high level at 6 h and declined at 12 h, respectively. Similar to CCK-AR mRNA, the expression of CCK-BR mRNA peaked at 2 h and kept a high level at 6 h, but it did not change at the first 0.5 h and was stable at a high level at 12 h.
CONCLUSION: The above results indicate that endogenous and exogenous sCCK-8 may significantly improve cardiac function and intractable hypotension of ES rats, which was likely related to high expression of CCK-A/BR in myocardium induced by LPS.