The present study was designed to demonstrate a hypothesis that some G-protein coupled receptors are up-regulated and a dysfunction of endothelium occurs in hypertension. The arteries from hypertensive patients and spontaneously hypertensive rats (SHR) were tested. An in vitro myograph system was used to obtain concentration–contraction curves mediated by endothelin ETA, endothelin ETB, 5-hydroxytryptamine 2A (5-HT2A)-receptors and α1-adrenoceptors in the arterial segments. In hypertensive patients, the maximum contractions (Emax) induced by endothelin ETB, endothelin ETA and 5-HT receptors were significantly increased with elevated pEC50 values, while a significantly leftward shift of α1-adrenoceptor-mediated contraction was seen. Similar results were obtained in SHR. Specific antagonists for 5-HT2A receptors or α1-adrenoceptors rightward shifted the concentration–contractile curves induced by 5-HT or noradrenalin, while the Emax were not significantly altered, suggesting that the contractions were mediated by 5-HT2A receptors and α1-adrenoceptors, respectively. Endothelium-dependent maximum relaxation (Rmax) in the arterial segments induced by acetylcholine was significantly decreased in both hypertensive patients and SHR. In addition, nitric oxide- and endothelium-derived hyperpolarizing factor-mediated dilatations were decreased significantly and the arterial endothelial cells were in part lost in SHR. In conclusion, endothelin ETB, endothelin ETA, 5-HT2A receptor- and alpha-adrenoceptor-mediated contractions were increased in hypertension, while the endothelium and its functions were damaged.