Abstract P080: Il-18 Potentiates Contractile Responses To Phenylephrine And Inhibits Relaxation Responses To Acetylcholine In Resistance Arteries From Wistar Rats

Abstract

Background: The etiology of essential hypertension remains unclear, and its mechanisms are complex. Indeed, low-grade inflammation and activation of the immune system have been implicated in hypertension. Clinical and population studies have consistently found increased circulating levels of interleukin 18 (IL-18) in patients with hypertension. Hypothesis: This study tests the hypothesis that IL-18 will enhance contractile responses to phenylephrine and impair relaxation responses to acetylcholine in isolated arterial rings from rats. Methods: Vascular function was performed on isolated pudendal arteries from male Wistar rats using wire myographs, kept in Krebs solution at 37°C, constantly aerated with 95%O 2 /5%CO 2 . Concentration-response curves to phenylephrine (PE; 10 -9 -3x10 -5 M), and acetylcholine (ACh; 10 -9 - 3x10 -5 M) were performed in the absence or in the presence of IL-18 (20ng/ml) for 1 hour and 6 hours respectively. Ten minutes prior to the incubation with IL-18, some arterial rings were incubated separately with the mitogen-activated protein kinase (MKK / MEK) inhibitor, PD98059 (10 -5 M). Concentration-response curves were analyzed using non-linear regression analysis. Data are presented as mean ± S.E.M. Statistical significance set at p<0.05. Data analyzed with GraphPad Prism 9.2.0. Results: In the pudendal arterial rings, the potency of PE was increased in the presence of IL-18 (pEC 50 6.510 ± 0.3987 vs 6.022 ± 0.2738 for control; p = 0.0268), Incubation with IL-18 plus PD98059 restored the contraction to PE to control levels. (pEC 50 6.105 ± 0.4007 vs 6.170 ± 0.2847 for control; p = 0.7120). Relaxation responses to Ach were impaired by incubation with IL-18 for 6 hours (pEC 50 5.942 ± 0.1575 vs 7.341 ± 0.1796 for control; p=0.0042) Conclusion: Our results show that IL-18 enhances the contractile responses to PE in pudendal arteries from Wistar rats by activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Thus, IL-18 may contribute to the increased vascular resistance characteristic of hypertension.