Angiotensin‐(1‐7) Prevents Angiotensin II‐induced Fibrosis in Cremaster Microvessels. (January 2015)

• Record Type: Journal Article
• Authors: Carver, Kyle A.; Smith, Thomas L.; Gallagher, Patricia E.; Tallant, E. Ann
• Is Part Of: Microcirculation. Volume 22:Number 1(2015:Jan.)
• Page Start: 19
• Page End: 27
• Publication Date: 2015-01
• Subjects: Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12159
• Languages: English
• ISSNs: 1073-9688

Abstract

<abstract abstract-type="main" id="micc12159-abs-0001"> <title>Abstract</title> <sec id="micc12159-sec-0001" sec-type="section"> <title>Objective</title> <p>The effect of the heptapeptide hormone Ang‐(1‐7) on microvascular fibrosis in rats with Ang II‐induced hypertension was investigated, since vascular fibrosis/remodeling plays a prominent role in hypertension‐induced end‐organ damage and Ang‐(1‐7) inhibits vascular growth and fibrosis.</p> </sec> <sec id="micc12159-sec-0002" sec-type="section"> <title>Methods</title> <p>Fibrosis of cremaster microvessels was studied in male Lewis rats infused with Ang II and/or Ang‐(1‐7).</p> </sec> <sec id="micc12159-sec-0003" sec-type="section"> <title>Results</title> <p>Ang II elevated systolic blood pressure by approximately 40 mmHg, while blood pressure was not changed by Ang‐(1‐7). Ang II increased perivascular fibrosis surrounding 20–50 <italic>μ</italic>m arterioles as well as interstitial fibrosis; coadministration of Ang‐(1‐7) prevented the increases in fibrosis. The fibrotic factor CTGF and phospho‐Smad 2/3, which upregulates CTGF, were increased by Ang II; this effect was prevented by coadministration of Ang‐(1‐7). Although TGF‐<italic>β</italic> phosphorylates Smad 2/3, TGF‐<italic>β</italic> was no different among treatment groups. In contrast, Ang II increased the MAP kinase phospho‐ERK1/2, which also phosphorylates Smad; p‐ERK was reduced by Ang‐(1‐7). Ang‐(1‐7), in the presence or absence of Ang II, upregulated the MAP kinase phosphatase DUSP1.</p> </sec> <sec id="micc12159-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These results suggest that Ang‐(1‐7) increases DUSP1 to reduce MAP kinase/Smad/CTGF signaling and decrease fibrosis in resistance arterioles, to attenuate end‐organ damage associated with chronic hypertension.</p> </sec> </abstract>