In spontaneously hypertensive rats (SHR), endothelium-dependent relaxations to acetylcholine are reduced compared to normotensive Wistar-Kyoto rats (WKY). Rings of thoracic aorta with and without endothelium were studied. Acetylcholine caused endothelium-dependent contractions in SHR rings but not in WKY rings. These contractions were inhibited by atropine but not by hexamethonium, and were prevented by inhibitors of phospholipase A₂ or cyclooxygenase, but not by inhibitors of prostacyclin synthetase, thromboxane synthetase, or leukotriene synthetase. Prostaglandins D₂, E₁, E₂, and F₂α caused concentration-dependent contractions in rings without endothelium from both strains. Endothelium-dependent relaxations to acetylcholine were significantly depressed in SHR compared to WKY. Indomethacin normalized these relaxations in SHR. The study suggests that acetylcholine activates muscarinic receptors in SHR aorta, leading to endothelium-dependent contractions mediated by cyclooxygenase products other than prostacyclin or thromboxane A₂. The reduced relaxations in SHR are likely due to simultaneous release of endothelium-derived contracting substances rather than decreased release of relaxing factors. The findings indicate that the endothelium in SHR may release both relaxing and contracting substances, contributing to the altered vascular response in hypertension. The study highlights the complex role of the endothelium in vascular regulation and the impact of hypertension on endothelial function.In spontaneously hypertensive rats (SHR), endothelium-dependent relaxations to acetylcholine are reduced compared to normotensive Wistar-Kyoto rats (WKY). Rings of thoracic aorta with and without endothelium were studied. Acetylcholine caused endothelium-dependent contractions in SHR rings but not in WKY rings. These contractions were inhibited by atropine but not by hexamethonium, and were prevented by inhibitors of phospholipase A₂ or cyclooxygenase, but not by inhibitors of prostacyclin synthetase, thromboxane synthetase, or leukotriene synthetase. Prostaglandins D₂, E₁, E₂, and F₂α caused concentration-dependent contractions in rings without endothelium from both strains. Endothelium-dependent relaxations to acetylcholine were significantly depressed in SHR compared to WKY. Indomethacin normalized these relaxations in SHR. The study suggests that acetylcholine activates muscarinic receptors in SHR aorta, leading to endothelium-dependent contractions mediated by cyclooxygenase products other than prostacyclin or thromboxane A₂. The reduced relaxations in SHR are likely due to simultaneous release of endothelium-derived contracting substances rather than decreased release of relaxing factors. The findings indicate that the endothelium in SHR may release both relaxing and contracting substances, contributing to the altered vascular response in hypertension. The study highlights the complex role of the endothelium in vascular regulation and the impact of hypertension on endothelial function.