Endothelium-Derived Hyperpolarizing Factor (EDHF) Mediates Acetylsalicylic Acid (Aspirin) Vasodilation of Pregnant Rat Mesenteric Arteries

Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found outdiscovered the molecular mechanism underlying this action. Aspirin (10(-12)-10(-6) M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 x 10(-4) M); (b) cyclooxygenase (Indomethacin, 10(-5) M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10(-7) M), intermediate conductance (IKca, TRAM34, 10(-5) M), and big conductance (BKca, paxilline, 10(-5) M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p < 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension.

Automated summary

The study demonstrates that aspirin induces vasodilation in mesenteric resistance arteries by acting through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. This mechanism suggests that aspirin may be beneficial for pregnancies complicated by hypertension by reducing peripheral vascular resistance.