Discussion showed biphasic contractions; consist of phasic contractions followed by tonic contractions as slow

4. Discussion showed biphasic contractions; consist of phasic contractions followed by tonic contractions as slow

4.1 Patterns of Ileal Strip Responses to Aspirin waves in these muscles, while the high concentrations

One of the finding in this study is that the ileal of aspirin showed complete relaxation of the ileal smooth muscles respond to different concentrations of

smooth muscles. The stimulator effects of aspirin on aspirin in different patterns in a dose response manner.

smooth muscles may be either related to the increasing These types of drugs relaxed the activities of the

of the extracellular Ca +2 influxes or increasing its smooth muscles through increasing the cellular

release form intracellular stores, whereas the inhibitor content of the cAMP, which leads to protein kinase +2 effects of aspirin may be caused by Ca influx

activation for different enzymes phosphorelation and

inhibition.

activity modification, were as its contraction The results of the present study are consistent with stimulation may either by release of Ca +2 or its storing

another study, in which low concentrations of aspirin in its internal stores [13].

increased the risk of hypertension, but high concentrations did not further increase the risk of

4.2 Effects of Aspirin Concentrations hypertension, through its different effect pattern on

In this study the low concentrations of aspirin blood vessels smooth muscles [14]. In previous study showed tonic contractions effect on these muscles,

aspirin showed antagonistic action on calcium this effect may be related to the increasing of internal

channels, and inhibition of cyclic COX-1 by acetyl free Ca +2 . The moderate aspirin concentrations choline group of serine compound [15]. The relax

Biphasic Response of Mouse Ileal Smooth Muscles to Aspirin in a Dose Response Manner

action of aspirin exerted through inhibition of the protein function at the posttranslational level. Recent RhoA/Rho-kinase activation, a critical component of

studies have reported that aspirin is able to acetylate vascular tone regulation through phosphorylation and

several other targets in addition to COX isoenzymes inhibition of MLCP [6].

[11]. These acetylation reactions may explain many In another study aspirin concentrations 25 μM, 50

hitherto unexplained effects of aspirin. μM and 100 μM in a dose-dependently antagonized

On basal tone and Calcium induced contractions in the vasoconstriction caused by transmembrane nerve

the human and guinea-pig tracheal muscle, the stimulation TNS and by nor epinephrine NE (from

cyclooxygenase inhibitors, indomethacin and aspirin

0.01 μM to 10 μM), this demonstrate that the usually increased spontaneous tone or Ca induced NO-releasing derivative of aspirin, NCX 4016, contractions in human strips, while consistently reduces vasoconstriction due to TNS at various

decreased tension development in the guinea-pig frequencies and prevents the effect of different

muscle. It is concluded that active tone in the two concentrations of NE in perfused rat tail artery

different tracheal muscles were controlled by different preparations with intact endothelium [7].

processes; that different arachidonate by-products may Cyclic GMP is considered to be an important

exert an effect ton basal tone in the two different regulator of smooth muscles function, and the action

muscles; and that different plasma membrane calcium of NO-containing vasodilators seems to be mediated

channels may be operative under basal conditions in by cyclic GMP. Although the mechanism of action of

the different muscles [18].

this cyclic nucleotide is unknown, studies in several

5. Conclusion

laboratories have demonstrated that cyclic GMP lowers intracellular Ca 2+ in agonist-treated and

The present study indicated that Aspirin exerted depolarized smooth muscles [16]. Also seen in rat

different effects on ileal smooth muscles contraction depending upon concentration. Low and moderate

aortic smooth muscles that acetylsalicylic acid not concentrations 2-40 mM had an active effect, while

only may modulate aortic smooth muscle contractility high concentrations 60-200 mM had inhibitory effect,

through the metabolites of arachidonic acid but may which led to relaxation. Free calcium solution

repair to a great extent the hypertension associated abolished muscles response to aspirin with the

plasma membrane permeability defect of vascular concentration which caused contraction. Aspirin in myocytes [9]. Aspirin acts as an acetylating agent turn led to continuation of acetylcholine induced where an acetyl group is covalently attached to a

contraction.

serine residue in the active site of the PTGS enzyme.