title: Enhanced G-protein coupled receptors-mediated contraction and reduced endothelium-dependent relaxation in hypertension.
abstract: 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 ET(A), endothelin ET(B), 5-hydroxytryptamine 2A (5-HT2A)-receptors and alpha1-adrenoceptors in the arterial segments. In hypertensive patients, the maximum contractions (Emax) induced by endothelin ET(B), endothelin ET(A) and 5-HT receptors were significantly increased with elevated pEC50 values, while a significantly leftward shift of alpha1-adrenoceptor-mediated contraction was seen. Similar results were obtained in SHR. Specific antagonists for 5-HT2A receptors or alpha1-adrenoceptors rightward shifted the concentration-contractile curves induced by 5-HT or noradrenaline, while the Emax were not significantly altered, suggesting that the contractions were mediated by 5-HT2A receptors and alpha1-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 ET(B), endothelin ET(A), 5-HT2A receptor- and alpha-adrenoceptor-mediated contractions were increased in hypertension, while the endothelium and its functions were damaged.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, and Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi, 710061, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Cang-Bao
authors.initials: CB
authors.lastname: Xu
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000368:Aged; D000818:Animals; D001158:Arteries / Q000187:drug effects; D016022:Case-Control Studies; D003106:Colon / Q000098:blood supply; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000648:ultrastructure; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D043562:Receptors, G-Protein-Coupled; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists