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Pellenc, Quentin; El Bitar, Sandy; Darmon, Arthur; Dupont, Sébastien; Michel, Jean-Baptiste; Jondeau, Guillaume

Smooth Muscle Cell Relaxation Worsens Aortic Dilatation and Clinical Presentation in a BAPN/Angiotensin II-Induced Aortic Dissection Model in Rats

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  • Media type: E-Article
  • Title: Smooth Muscle Cell Relaxation Worsens Aortic Dilatation and Clinical Presentation in a BAPN/Angiotensin II-Induced Aortic Dissection Model in Rats
  • Contributor: Pellenc, Quentin; El Bitar, Sandy; Darmon, Arthur; Dupont, Sébastien; Michel, Jean-Baptiste; Jondeau, Guillaume
  • imprint: S. Karger AG, 2022
  • Published in: Journal of Vascular Research
  • Language: English
  • DOI: 10.1159/000526417
  • ISSN: 1018-1172; 1423-0135
  • Keywords: Cardiology and Cardiovascular Medicine ; Physiology
  • Origination:
  • Footnote:
  • Description: <jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Beta-aminopropionitrile (BAPN) administration is a chemically induced model for preclinical aortic pathologies research. Angiotensin II (AngII) has been widely used to promotes aortic dissections in mice. Here, we provide insight on a modified aortic dissection model in rats. The effect of smooth muscle cell (SMC) relaxation with vasodilators is studied in this model. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Forty Sprague-Dawley rats were divided in 4 groups: control, isosorbide dinitrate (ISDN, 30 mg/kg/day) in the drinking water, BAPN (0.02%) in the food, BAPN + ISDN (same doses). Thoracic and abdominal aortic diameters were evaluated through transthoracic ultrasound echography. After 6 weeks, all rats were infused with AngII (1 mg/kg/day) subcutaneously. Survival and type of aortic events were numbered. Histological and histochemical analyses of aorta were performed. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Initial telesystolic ascending aorta diameters were equal in all groups and became significantly larger in the BAPN + ISDN group compared to the BAPN group (control: 3.37 ± 0.17 mm, ISDN: 3.49 ± 0.16 mm, BAPN: 3.53 ± 0.13 mm, BAPN + ISDN: 3.61 ± 0.16 mm, analysis of variance &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.0001). BAPN followed by AngII infusion showed a significant lower survival rate (&lt;i&gt;p&lt;/i&gt; = 0.029) and produced a large panel of aortic events. Association of ISDN and BAPN significantly reduces survival (&lt;i&gt;p&lt;/i&gt; = 0.001) and provides more aortic events compared to BAPN alone (&lt;i&gt;p&lt;/i&gt; = 0.031). In both BAPN-treated groups, orcein staining revealed split and dissected elastic fibers in the media, alcian blue staining showed mucoid degeneration of the aortic wall, and Perls-diaminobenzidine staining revealed an accumulation of Fe&lt;sup&gt;2+&lt;/sup&gt;. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; SMC relaxation with ISDN increases aortic dilatation, worsens aortic prognosis, and reproduces human histological findings in a low-dose BAPN/AngII-induced aortic dissection model in rats. </jats:p>