p-Coumaric acid reduces high glucose-mediated impairment of endothelium-dependent relaxation in rat aorta

p-Coumaric acid (p-CA) is an ubiquitous plant metabolite with antioxidant, anti-inflammatory, and anticancer properties. The present study was designed to evaluate the preventive effects of p-CA on endothelium-dependent impairment produced by high glucose (HG) (D-Glucose 25 mM) in isolated rat thoracic aorta. Aortic rings obtained from male Sprague-Dawley rats were mounted in an organ bath and pretreated for 3 h with D-Glucose 5 mM, HG and HG plus p-CA (1, 10 and 100 μM). After this period of time endotheliumdependent relaxation was tested by cumulative addition of acetylcholine (ACh) in pre-contracted rings with phenylephrine (PE) (0.1 μM). P-CA elicited a moderate endothelium-dependent vasodilatory effect (Emax= 29.28 ± 1.89%, N=6; pD₂= 6.075 ± 0.184, N=6). When aortic rings were pre-incubated for 3 h with HG, Emax for ACh decreased dramatically from 87.69 ± 2.59% (N=6) to 40.54 ± 1.78% (N=6). The negative effect of HG was partially reverted in rings co-incubated with p-CA in a concentration-dependent manner as shown for Emax values to each p-CA concentration: 1 μM (48.57 ± 1.82%), 10 μM (60.81 ± 1.80%) and 100 μM (64.51 ± 1.80%). The action of p-CA was associated with a significant change in Emax. No statistical difference in pD₂ was observed. Our results clearly show that p-CA protect ACh-induced endothelial-dependent relaxation affected by HG in isolated rat aortic rings.