Effect Of Selective Blockade CGMP-dependent Protein Kinase On The Systolic Function Of Rats' Vascular Rings Incubated With LPS

Objective: To investigate the role of selective blockade cGMP-dependent protein kinase (PKG) on recovery contractility of the rat aortic rings incubated with lipopolysaccharide (LPS). And to compare the effect of two kinds of specific PKG inhibitor DT-2 and (D)-DT-2 on the systolic function of rats'vascular rings incubated with LPS.Methods: The experiment was performed in two parts. Partâ… : The SD rat thoracic aortic rings were randomly divided into four groups as follows: Control group(saline), LPS group(LPS 75μg/mL), LNAME group (LPS 75μg/mL +L-NAME 10^-1mmol/L) and DT2 group (LPS 75μg/mL+DT-2 2×10^-3mmol/L). Meanwhile the contractive concentration response curves of vascular rings, E_max and EC₅₀ of each group of vascular rings to phenylephrine (PE) were measured at different times (2h, 3h, 4h) in vitro. Partâ…¡: First, the SD rat thoracic aortic rings were randomized into three groups as follows (n=5): Saline group, DT2 group and DDT2 group. After dilating the blood vessels with 5×10^-2mmol/L of 8-Br-cGMP, above-mentioned drugs were added, and the tension changes of vascular rings were measured. Then the rat thoracic aortic rings were divided into Control group, LPS group, LPS-DT2 group and LPS-DDT2 group randomly. After incubation with LPS for 3h in vitro, the vascular contractive concentration response curves to PE of vascular rings was drawn in each group, the E_max and EC₅₀ were compared among groups.Results: In partâ… : The contractive concentration response curve of vascular rings incubated with LPS was significantly lower compared with control group (P<0.05). L-NAME effectively improved the vascular systolic function after incubation with LPS for 2h,3h and 4h; the EC₅₀, E_max were of significant difference compared with LPS group (P<0.05). DT2 significantly enhanced the contractile function of vascular rings after incubation with LPS for 3h(P<0.01); EC₅₀, E_max were of significant difference compared with LPS group (P<0.01); however, the concentration response curve of DT2 group had no significant difference compared with LPS group at 2h or 4h. In partâ…¡, Both of PKG inhibitor DT-2 and (D)-DT-2 can contract the 8-Br-cGMP-dilated vascular rings, and the E_max in DDT2 group was higher than that in the DT2 group (P<0.05). DT-2 and (D)-DT-2 can significantly improve the contractile function of vascular rings after exposured LPS for 3h (P<0.01), and their E_max, EC₅₀ were significant different from those of LPS group (P<0.01). When compared with LPS-DT2 group, the E_max in LPS-DDT2 group increased significantly and the EC₅₀ reduced remarkably (P<0.05).Conclusion: Selective blockade of cGMP-dependent protein kinase (PKG) can partially recover systolic function of the rat aortic rings being incubated with LPS. And the efficacy of (D)-DT-2 of recovering the vascular reactivity is stronger than DT-2.