Does spironolactone prevent Ang II-induced structural and mechanical changes in resistance arteries in male Sprague-Dawley rats?
Spironolactone partially prevents Ang II-induced vascular structural and mechanical alterations in rats independently of blood pressure reduction, suggesting aldosterone mediates some Ang II effects on resistance arteries.
BACKGROUND: Angiotensin (Ang) II stimulates aldosterone production, which may mediate some of the effects of Ang II. OBJECTIVE: To test whether Ang II-induced structural and mechanical changes in resistance arteries may be prevented by the non-selective aldosterone receptor blocker, spironolactone, independently of reduction in blood pressure. METHODS: Male Sprague-Dawley rats received Ang II 120 ng/kg per min subcutaneously (s.c.) with or without spironolactone or hydralazine (25 mg/kg per day). Two additional groups received aldosterone (750 ng/h s.c.) with or without spironolactone. After 2 weeks, third-order mesenteric arteries were dissected and studied by pressurized myograph. Deposition of collagen type I/III in the vascular wall was evaluated by confocal immunofluorescence microscopy. RESULTS: Ang II increased blood pressure significantly (P <0.01); this was partially prevented by spironolactone (P <0.01) and nearly normalized by hydralazine (P <0.01). Media thickness, media:lumen ratio and media cross-sectional area of mesenteric resistance arteries increased under Ang II or aldosterone (P <0.01) and this was partially prevented by spironolactone (P <0.01), but not by hydralazine. Compared with the control or Ang II + spironolactone groups, rats treated with Ang II with or without hydralazine presented stiffer vessels, with leftward shift of the stress-strain relationship and a raised slope of the incremental elastic modulus-stress relationship (P <0.05). Confocal microscopy demonstrated enhanced deposition of collagen type I/III in the media of arteries from rats infused with Ang II or aldosterone, an effect that was prevented partially by spironolactone but unaffected by hydralazine. CONCLUSION: Ang II-induced vascular alterations in structure, mechanics and composition were partially prevented by spironolactone, independently of blood pressure reduction, providing further evidence that some actions of Ang II on resistance arteries are mediated by aldosterone.
Neves et al. (Wed,) studied this question.
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