Abstract 530: Vascular Remodeling by Angiotensin Peptide Hormones Alters Reactivity of the Microcirculation
Endothelial dysfunction associated with hypertension leads to end-organ damage through impairment in tissue perfusion. Angiotensin II (Ang II) causes vascular remodeling and fibrotic stiffening and attenuates endothelial-dependent vasorelaxation. However, the heptapeptide hormone angiotensin-(1-7) [Ang-(1-7)] reduces the structural effects of Ang II and acutely vasodilates vessels ex vivo. Lewis rats were chronically treated with either Ang II, Ang-(1-7), or both angiotensin peptides to examine the effect of the peptide hormones on microvascular remodeling and reactivity of cremaster muscle arterioles in vivo. Cremaster arterioles (50 microns in diameter) were visualized by intravital microscopy to measure vascular reactivity. Ang II elevated systolic blood pressure by 43 mmHg, an effect that was not changed by co-administration of Ang-(1-7); Ang-(1-7) alone had no effect. Ang II increased the media to lumen ratio (by 82% compared to Sham, n=7, p<0.01) and perivascular fibrosis (by 133% compared to Sham, n=7, p<0.001), while co-treatment with Ang-(1-7) attenuated the Ang II-enhanced remodeling and fibrosis to values no different than Sham or Ang-(1-7) alone. Phenylephrine (PE) elicited vasoconstriction in Sham rats, reducing vessel diameter by 21%, and this effect was not altered in rats treated with Ang II. Although PE-constricted arterioles from Sham rats vasodilated in response to acetylcholine (Ach, a 31.4% increase in diameter), vessels from Ang II-treated rats had a blunted response to Ach (a 9% increase). These results suggest that the Ang II-mediated microvascular remodeling altered microvascular vasodilation. In contrast, arterioles from rats treated with Ang-(1-7) or the combination of Ang-(1-7) and Ang II did not constrict in response to PE or endothelin. However, acute administration of the nitric oxide synthase inhibitor L-NAME to Ang-(1-7)-treated rats restored the vasoconstrictive response to PE, indicating that Ang-(1-7) increases endogenous nitric oxide to maximally dilate microvascular arterioles and prevent constriction. These results suggest Ang-(1-7) may serve as an effective adjuvant therapy to attenuate end-organ damage by increasing blood flow and tissue perfusion caused by hypertension.
- © 2012 by American Heart Association, Inc.