Smooth Muscle Relaxation by Ibuprofen and Diclofenac: In Vitro Models Reveal Differences in Their Modes of Action?

• Published in: Digestive diseases and sciences Vol. 59; no. 8; p. 1651
• Main Authors: Callingham, B.A, Gilliver, R.L, Jaker, S, Milton, A.S, Rainsford, K.D
• Format: Journal Article
• Language: English
• Published: Springer 23.05.2022
• Subjects: Analysis; Heart attack; Ibuprofen; Smooth muscle
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-014-3278-0

Changes in vascular contractility, associated with non steroidal anti-inflammatory drugs (NSAIDs) (1), are important in the pathogenesis of gastro-duodenal mucosal injury and cardiovascular pathology (e.g. myocardial infarction). Previously (2), it has been found that NSAIDs vary in their relaxant or contractile effects on smooth muscle preparations and deer digital arterial blood vessels stimulated with agonists (e.g. 5-hydroxytryptamine and phenylephrine). Ibuprofen and diclofenac were amongst the NSAIDs that produced relaxation (2). In the present studies we have investigated the mechanisms of the receptor-mediated and intracellular transduction involved, using electrically-stimulated contractions of the fallow deer digital artery, as well as the rat anoccocygeus smooth muscle and guinea pig ileum, as previously described (2). Rac-, R(-) and S(+)-ibuprofen as well as diclofenac all relaxed electrically-stimulated deer arteries; diclofenac and R(-)-ibuprofen being the most potent. Removal of endothelium, inhibition of COX isoenzymes, e/iNOS, soluble guanylate cyclase, phosphodiesterase and KATP conductance all failed to affect the actions of diclofenac and rac-ibuprofen. However, inhibition of [K.sup.+] conductance attenuated the response to both these drugs. In addition, data supporting the relaxant effects of diclofenac and rac-ibuprofen were obtained from the smooth muscle preparations. In conclusion, the results show that diclofenac and rac-ibuprofen reduce electrically-stimulated vascular and smooth muscle contraction by an increase in [K.sup.+]--conductance or other [K.sup.+]-channel-mediated systems. The actions of these NSAIDs may be relevant to their gastro-duodenal and cardiovascular adverse reactions and raise prospects for the development of agents to prevent the vascular side effects of NSAIDs.