Reconstitution of autophagy ameliorates vascular function and arterial stiffening in spontaneously hypertensive rats

Cameron G. McCarthy, Camilla F. Wenceslau, Fabiano B. Calmasini, Nicole S. Klee, Michael W. Brands, Bina Joe, R. Clinton Webb

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Insufficient autophagy has been proposed as a mechanism of cellular aging, as this leads to the accumulation of dysfunctional macromolecules and organelles. Premature vascular aging occurs in hypertension. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in clinical and experimental hypertension. Previously, we have reported decreased autophagy in arteries from spontaneously hypertensive rats (SHRs); however, the effects of restoring autophagic activity on blood pressure and vascular function are currently unknown. We hypothesized that reconstitution of arterial autophagy in SHRs would decrease blood pressure and improve endothelium-dependent relaxation. We treated 14- to 18-wk-old Wistar rats (n= 7 vehicle and n= 8 trehalose) and SHRs (n= 7/group) with autophagy activator trehalose (2% in drinking water) for 28 days. Blood pressure was measured by radiotelemetry, and vascular function and structure were measured in isolated mesenteric resistance arteries (MRAs) using wire and pressure myographs, respectively. Treatment with trehalose had no effect on blood pressure in SHRs; however, isolated MRAs presented enhanced relaxation to acetylcholine, in a cyclooxygenase- and reactive oxygen species-dependent manner. Similarly, trehalose treatment shifted the relaxation to the Rho kinase (ROCK) inhibitor Y-27632 to the right, indicating reduced ROCK activity. Finally, trehalose treatment decreased arterial stiffness as indicated by the slope of the stress-strain curve. Overall these data indicate that reconstitution of arterial autophagy in SHRs improves endothelial and vascular smooth muscle function, which could synergize to prevent stiffening. As a result, restoration of autophagic activity could be a novel therapeutic for premature vascular aging in hypertension.

Original languageEnglish (US)
Pages (from-to)H1013-H1027
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume317
Issue number5
DOIs
StatePublished - Jan 1 2019

Keywords

  • Arterial stiffening
  • Autophagy
  • Hypertension
  • Vascular aging
  • Vascular function

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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