sincalide and Hypertension--Pulmonary

For investigation of the regulatory mechanism of cholecystokinin-octapeptide (CCK-8) on pulmonary circulation in rabbits with endotoxic shock (ES) induced by lipopolysaccharides (LPS), mean arterial pressure (MAP) and pulmonary arterial pressure (PAP) were evaluated for 5 h in five groups of rabbits: group of LPS (8 mg/kg, i.v.)-induced ES, group of CCK-8 pretreatment (15 microg/kg, i.v.) 15 min before LPS administration (8 mg/kg, i.v.), group of proglumide pretreatment (1 mg/kg, i.v.) 15 min before LPS administration (8 mg/kg, i.v.), group of CCK (15 microg/kg, i.v.) only, and normal saline (control) group. The pulmonary arterial tension was measured with isolated vascular ring technique. The results showed that LPS-induced pulmonary arterial hypertension was abolished by CCK-8. In contrast, proglumide, a nonspecific antagonist of CCK-8 receptor, potentiated the deleterious effect of LPS. The contractile response of isolated pulmonary artery to alpha-adrenoceptor agonist phenylephrine (PE) was enhanced and the relaxation response to acetylcholine (ACh) was depressed significantly after LPS was injected, but the effect could be reversed by CCK-8. These results suggest that pulmonary circulation is improved by CCK-8 in ES, and the regulatory effects of CCK-8 may be brought about by modulating the pulmonary arterial tension.

Topics: Animals; Hypertension, Pulmonary; Male; Pulmonary Artery; Rabbits; Shock, Septic; Sincalide; Vasodilation

To explore the mechanism underlying cholecystokinin-octapeptide (CCK-8) induced attenuation of pulmonary arterial hypertension (PAH) in endotoxic shock, the effects of CCK-8 on the changes in rabbit pulmonary arterial reactivity induced by tumor necrosis factor-alpha (TNF-alpha) were observed with the isolated arterial ring technique, and the ultrastructure of pulmonary arterial endothelium was observed under a scanning electron microscope. The contractile response to -adrenoceptor agonist phenylephrine (PE), the endothelium-dependent relaxation response to acetylcholine (ACh) and the endothelium-independent relaxation response to sodium nitroprusside (SNP) were not affected by TNF-alpha (4000 U/ml) after incubation for 2 h, while, if the incubation time was prolonged to 7 or 14 h, the relaxation response of pulmonary artery to ACh was depressed significantly, which, however, could be reversed by concomitant exposure to CCK-8 (0.5 microgram/ml). Incubation of pulmonary artery with CCK-8 (0.5 microgram/ml) alone did not bring out any contractile responses. Moreover, CCK-8 (0.5 microgram/ml) alleviated the ultrastructural lesions induced by TNF-alpha (4000 U/ml). These results suggest that CCK could protect pulmonary arterial endothelium against the detrimental effects by TNF-alpha.

Topics: Animals; Endothelium, Vascular; Female; Hypertension, Pulmonary; In Vitro Techniques; Male; Pulmonary Artery; Rabbits; Sincalide; Tumor Necrosis Factor-alpha; Vasodilation