title: Maturation reveals a decrease in endothelium-dependent contraction induced by depolarization in the aorta of spontaneously hypertensive rats.
abstract: The influence of the endothelium on aortic contractility to KCl 100 mM was studied during maturation and aging in normotensive Wistar and spontaneously hypertensive rats (SHR). In Wistar rats, there was no significant difference in maximal responses in the course of aging whether the endothelium was present (E+) or not (E-). A similar result was obtained in SHR E- rings. However, contraction was significantly higher in E+ rings of young (9 weeks) compared to adult and old SHR (18, 25, 36 and 72 weeks) (in mN/mm2: 34.8 +/- 3.1 versus 24.8 +/- 1.8, 16.0 +/- 2.5, 17.4 +/- 2.0 and 12.9 +/- 1.8, p<0.01). This increase remained significant in 18- compared to that of 25-, 36- and 72-week-old rats (p<0.01). No change appeared with age in noradrenaline-induced contractions of E+ rings neither in Wistar nor in SHR. A dose-dependent decrease in response to KCl was observed after an in vivo pretreatment of the young SHR with acetylsalicylic acid. Finally, blocking the TXA2/PGH2 receptor by addition of GR 32191B or ONO-3708 led to a decrease in the response of young SHR aortic rings to KCl. This study points out a decrease in the response of SHR aortic rings to a depolarizing agent during maturation. The enhanced contraction observed in young SHR seems to be the result of an increased participation of an endothelium-derived, cyclooxygenase-dependent contracting factor(s), most likely either TXA2 or PGH2. This factor might play a key role in the onset of hypertension in the spontaneously hypertensive strain.
authors.affiliation: Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, CNRS UMR 7034, Faculté de Pharmacie, Université Louis Pasteur, Illkirch, France. matz@pharma.u-strasbg.fr
authors.forename: R L
authors.initials: RL
authors.lastname: Matz
authors.forename: B
authors.initials: B
authors.lastname: Van Overloop
authors.forename: E
authors.initials: E
authors.lastname: Gaubert
authors.forename: A
authors.initials: A
authors.lastname: Gairard
mesh_terms: D000375:Aging; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001241:Aspirin / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001835:Body Weight; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006538:Heptanoic Acids / Q000494:pharmacology; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D011448:Prostaglandin Antagonists; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2; D011189:Potassium Chloride; C049855:ONO 3708; C060013:vapiprost; D001241:Aspirin; D009638:Norepinephrine