title: Resistance artery mechanics and composition in angiotensin II-infused mice: effects of cyclooxygenase-1 inhibition.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of cyclooxygenase (COX)-1 on vascular alterations in structure, mechanics, and extracellular matrix (ECM) components induced by angiotensin (Ang) II in mesenteric arteries from wild-type (WT) and COX-1 knockout (COX-1(-/-)) mice.
  
  
  RESULTS
  Animals were infused with vehicle or Ang II (400 ng/kg/min, s.c.) ± SC-560 (COX-1 inhibitor), DFU (COX-2 inhibitor), or SQ-29548 (TP receptor antagonist). After 2 weeks, vessels were isolated and exposed to intraluminal pressures (3-140 mmHg, pressurized myograph) to determine mechanical properties. Angiotensin II-induced vascular hypertrophic remodelling in WT was reversed by SC-560 or SQ-29548, but unaffected by DFU. Angiotensin II increased vessel stiffness (P< 0.01), this effect being ameliorated by SC-560 or SQ-29548, but unmodified by DFU. Angiotensin II failed to modify vessel elasticity in COX-1(-/-) mice. In WT vessels, Ang II enhanced COX-1 immunostaining, induced collagen and fibronectin depositions and decreased elastin content (P< 0.01). These effects were reversed by SC-560 or SQ-29548, but unaffected by DFU. In COX-1(-/-) mice, Ang II did not affect ECM contents. In WT, Ang II increased COX-1 and decreased COX-2 expression, and enhanced the vascular release of 6-keto-PGF1α which was prevented by COX-1 blockade. Human coronary artery smooth muscle cells, incubated with Ang II, showed an increased expression of procollagen I, which was abrogated by SC-560 or SQ-29548.
  
  
  CONCLUSIONS
  Angiotensin II-induced alterations of resistance arteries in structure, mechanics, and ECM composition were prevented by COX-1 inhibition and TP receptor antagonism, indicating that Ang II-mediated vascular damage is mediated by COX-1-derived prostanoid prostacyclin, activating TP receptors.
authors: Department of Internal Medicine, University of Pisa, Pisa, Italy. agostino.virdis@med.unipi.it
authors: Agostino
authors: A
authors: Virdis
authors: Rocchina
authors: R
authors: Colucci
authors: Mario Fritsch
authors: MF
authors: Neves
authors: Ilaria
authors: I
authors: Rugani
authors: Fatma
authors: F
authors: Aydinoglu
authors: Matteo
authors: M
authors: Fornai
authors: Chiara
authors: C
authors: Ippolito
authors: Luca
authors: L
authors: Antonioli
authors: Emiliano
authors: E
authors: Duranti
authors: Anna
authors: A
authors: Solini
authors: Nunzia
authors: N
authors: Bernardini
authors: Corrado
authors: C
authors: Blandizzi
authors: Stefano
authors: S
authors: Taddei