Influence of cyclic guanosine 3',5' monophosphate modulators on muscle contraction of rat aortas

OBJECTIVE: The study examined the influence of probenecid (Pn), sildenafil (Sd) and oxidiazoloquinoxalin (ODQ) on contraction of phenylephrine (PhE) stimulated rat aortas.

METHODS: The study was performed at Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany, from 1st July to 30th September 2005. Thirty-five isolated rat aortas were stimulated with 10 uM PhE or preincubated for 30 minutes with 10 uM Pn, or 10 uM ODQ, or 50 uM Sd, and then incubated with 10 uM PhE in the presence or absence of the substances. The phosphorylated myosin light chain 20 was detected by using an antibody against phosphomyosin light chain 2.

RESULTS: The ratio of PhE stimulated phosphorylation of aortas (p<0.05) to the untreated was 16.7:1 at 30 seconds and 20.4:1 at 60 seconds. The stimulation decreased significantly at 120 seconds then during the following 10 minutes. Pre-incubation with 50 uM Sd (p>0.05) or 10 uM Pn (p<0.05) reduced the phosphorylation induced by PhE that was added to each for 30 seconds. But pre-incubation with 10 uM ODQ increased the phosphorylation brought about by addition of PhE for 60 seconds, p>0.05. The washout-effect of these modulators was not significant after stimulation with PhE only.

CONCLUSION: The study demonstrates the involvement of cyclic guanosine 3',5' monophosphate and its modulators on muscle contraction of rat aortas. Sildenafil and Pn reduced while oxidiazoloquinoxalin increased the contraction of rat aortas.