[Administration of hydrogen sulfide intraperitoneally reverses the hyporesponsiveness of rat pulmonary artery induced by lipopolysaccharide and its relationship with carbon monoxide].

OBJECTIVE

To explore the effect of hydrogen sulfide (H(2)S) on abnormal pulmonary artery reactivity induced by lipopolysaccharide (LPS) and its relationship with carbon monoxide (CO).

METHODS

Forty eight rats were divided into four groups randomly according to table of random number: control group (normal saline, NS), LPS group, a donor of H(2)S sodium hydrosulfide (NaHS)+LPS group, and NaHS+NS group (n=12 in each group). Rats were given LPS by intratracheal instillation (0.8 ml/kg). 0.5 ml of NaHS (28 μmol/kg) was injected intraperitoneally 10 minutes before LPS or NS instillation and 2 hours after LPS or NS instillation in NaHS+LPS and NaHS+NS groups. Twelve hours after instillation of LPS, 6 rats from each group were sacrificed. The pulmonary artery rings (PARs) were prepared and the changes in cumulative relaxation response of PARs to NaHS were detected before and after incubation with an inhibitor of heme oxygenase-1 (HO-1) zinc protoporphyrinIX (ZnPPIX) using isolated vascular ring tension detecting technique. Twelve hours after LPS instillation, the remaining 6 rats in each group were sacrificed, and the contents of carboxyhemoglobin (COHb) in efferent pulmonary blood (EPB) and afferent pulmonary blood (APB) were measured, and the difference between the contents of COHb in EPB and that of APB was calculated to represent content of CO from pulmonary circulation.

RESULTS

In the present study, compared with control group, after the instillation of LPS the percentage of relaxation response of PARs to NaHS was significantly declined [(75.72±7.22)% vs. (96.40±4.40)%, P<0.01]. After being incubated with ZnPPIX, the decreased relaxation response of PARs to NaHS induced by LPS was further depressed [(62.91±8.22)% vs. (75.72±7.22)%, P<0.01]. Administration of NaHS intraperitoneally reversed the hyporesponsiveness of PARs to NaHS, the percentage of relaxation response of PARs to NaHS was significantly increased [(94.65±8.45)% vs. (75.72±7.22)%, P<0.01]. However ZnPPIX also attenuated the effect [(83.75±9.76)% vs. (94.65±8.45)%, P<0.01]. NO significant changes were observed between NaHS+NS group and control group, also between the results before and after ZnPPIX incubation . Compared with control group, the difference between the contents of COHb in EPB and that of APB increased after instillation of LPS [(3.12±0.48)% vs. (2.12±0.32)%, P<0.05], which further increased after intraperitoneal administration of NaHS [(4.03±0.56)%, P<0.01].

CONCLUSION

The results suggested that intraperitoneal administration of H(2)S could reverse hyporesponsiveness of PARs to H(2)S induced by LPS, and the result might be related to an intensification of HO-1/CO system in pulmonary artery tissue.