title: Endothelium-dependent inhibition of the contractile response is decreased in aorta from aged and spontaneously hypertensive rats.
abstract: BACKGROUND
  Stimulation of vascular 5-hydroxytryptamine-2C (5-HT(2c)) receptors produces contraction in rat aorta. We investigated the effect of aging on endothelium-dependent inhibition of contractile responses in thoracic aorta from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Endothelium-intact and denuded aortic rings were prepared from young (7-9 weeks old) and senescent (65-70 weeks old) WKY and SHR rats. Changes in isometric tension elicited by 5-HT, in the absence or in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) or indomethacin were recorded.
  
  
  RESULTS
  In aorta from WKY and SHR, 5-HT elicited concentration-dependent contractions, which were increased by endothelium removal. The ability of endothelium to depress contractile response to 5-HT was found to be reduced in vessels from senescent animals, mainly in SHR. L-NAME increased the sensitivity and maximal effect to 5-HT in endothelium-intact but not in denuded aortic rings from young WKY rats. The effect of L-NAME was lower in young SHR compared with age-matched WKY rats, but it did not modify the response to 5-HT in senescent rats. Indomethacin did not affect contraction in arteries from young WKY or in denuded aortic rings from young SHR and aged WKY. In contrast, the inhibitor attenuated the response in endothelium-intact vessels from young SHR and aged WKY, and this effect was more marked in arteries with and without endothelium from senescent SHR. Thus, inhibition of cyclooxygenases by indomethacin revealed an enhanced endothelium-dependent modulation of contraction in senescent and hypertensive rats.
  
  
  CONCLUSIONS
  Results indicate that hypertension and aging decrease the negative modulator role of endothelium, in 5-HT-induced vasoconstriction in aorta from WKY and SHR. Data also point out that endothelial dysfunction involves an increased formation of vasoconstrictor prostanoids, which counteract nitric oxide effects. In addition, SHR endothelium releases contractile prostanoids at an early stage of hypertension, whereas in old SHR vascular smooth muscle also releases prostanoids, which contribute to 5-HT-induced contraction.
authors.affiliation: Laboratorio de Farmacología Cardiovascular, Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, México, México. maxibarrab@correo.unam.mx
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Ibarra
authors.forename: Juan Javier
authors.initials: JJ
authors.lastname: López-Guerrero
authors.forename: Ricardo
authors.initials: R
authors.lastname: Mejía-Zepeda
authors.forename: Rafael
authors.initials: R
authors.lastname: Villalobos-Molina
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004727:Endothelium / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012701:Serotonin / Q000494:pharmacology
chemical_list: D012701:Serotonin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin