| Cholecystokinin ( CCK ) widely takes part in different physiological and pathophysiological actions as neuropeptides in the central nervous system and the gastrointestinal tract, as well as hormones in the gastrointestinal tract. It is well known that CCK-receptor (CCK-R) was classified into two subtypes: CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR) .Previous studies showed that Cholecystokinin octapeptide (CCK-8), the predominant active fragment of endogenous CCK , had cardiovascular actions in both conscious and anesthetized animals, and elicited dose-dependant increase in arterial blood pressure and a variable change in heart rate (HR) . To exclude the effect of the central nervous system, a recent report was revealed by Gaw that injection of CCK-8 caused a dose-dependent increase in arterial blood pressure and a bradycardia in pithed rats, and the above effects of CCK-8 were inhibited by administration of CCK-AR antagonists, loxiglumide and devazepide, while not by treatment with CCK-BR antagonist, L-365,260. There are few reports about the effect of CCK-8 on vascular. Janssen et al. reported that i. v. administration of low dose of CCK-8 caused constrictions of renal, mesenteric and hindquarter arteries, while high dose of CCK-8 caused vasodilatations of the above arteries. The vasoreactivities of aorta, carotid and femoral arteries were unaffected by treatment with CCK-8 in rats in vitro.Lipopolysaccharide (LPS), the main component of bacterial endotoxin, can induce endotoxin shock (ES), which was verydangerous in clinic and the mortality was high. ES is associated with cardiac dysfunction and intractable low arterial pressure. Previous studies showed that the protein expresses of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) in myocardium could be induced by LPS. The reduction in cardiac function seen in ES appears to be due to the increase in the levels of nitric oxide (NO), carbon monoxide (CO), tumor necrosis factor-cc (TNF-a) and interleukin-lp (IL-lp) . A series studies of our department have found that endogenous and exogenous CCK-8 had anti-ES effect. CCK-8 had the ability to reverse the fall in mean artery pressure , and prevent the pulmonary artery hypertension(PAH), and attenuate the pathomorphological changes of main organs , and decrease the mortality. In contrast, pretreatment with proglumide, the nonselective CCK-receptor antagonist, could delay the recovery of blood pressure and the increase of mortality of ES rats. However, the effect of CCK-8 on cardiac function and its mechanism remain unclear.The characterized pathogenic changes in ES were the systemic vasodilatation and the hyporeactivity to vasoconstrictors. Previous studies indicated that the protein expresses of iNOS and HO-1 in vascular smooth muscle cells and endothelial cells, lead to increase in production of NO and CO. Furthermore, LPS per se could induce the oxidantive injury of artery. All of this could induce the hyporeactivity of artery. The studies of our department suggested that CCK-8 could partly reverse the increase of contractile response and the reduction of endothelium-dependent relaxation response of pulmonary artery, and the decrease of contractile response and the depression of endothelium-dependent relaxation response of aorta, which both incubated in vitro with LPS, but the precise mechanism remains elusive.Basing on the previous studies of our department, the purposes10of the present study was to examine the effect and its mechanism of CCK-8 on cardiac function and aortic hyporeactivity in ES rats. (1) Effects of different doses CCK-8 on cardiac function in anesthetized rats. (2) Effect of CCK-8 on cardiac function in ES rats. (3) Action of CCK-8 in alleviating myocardial injury of ES rats. (4) Action of CCK-8 inhibiting the protein express of iNOS and HO-1 in myocardium of ES rats. (5) Changes of CCK-R mRNA expression in myocardium of ES rats. (6) Effect of CCK-8 on aortic hyporeactivity of ES rats. (7) The mechanism of CCK-8 in reversing aortic hyporea...
|
PDF Full Text Request