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

• Main Authors: Helga Helgadóttir, Teresa Tropea, Sveinbjörn Gizurarson, Maurizio Mandalà
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: International Journal of Molecular Sciences
• Subjects: endothelial cells; smooth muscle cells; relaxation; pre-eclampsia; hypertension; calcium-activated potassium channels
• Online Access: https://www.mdpi.com/1422-0067/22/18/10162

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 × 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 (<i>p</i> < 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.