AIMS: 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. METHODS AND 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. CONCLUSION: 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.
AIMS: 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. METHODS AND 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. CONCLUSION: 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 prostanoidprostacyclin, activating TP receptors.
Authors: M S Avendaño; S Martínez-Revelles; A Aguado; M R Simões; M González-Amor; R Palacios; P Guillem-Llobat; D V Vassallo; L Vila; J García-Puig; L M Beltrán; M J Alonso; M V Cachofeiro; M Salaices; A M Briones Journal: Br J Pharmacol Date: 2016-03-21 Impact factor: 8.739
Authors: Marie Billaud; Alexander W Lohman; Adam C Straub; Thibaud Parpaite; Scott R Johnstone; Brant E Isakson Journal: Microcirculation Date: 2012-05 Impact factor: 2.628