Journal article
Angiotensin II‐induced endothelial dysfunction: Impact of sex, genetic background, and rho kinase
Physiological reports, Vol.10(11), pp.e15336-n/a
06/2022
DOI: 10.14814/phy2.15336
PMCID: PMC9184751
PMID: 35681278
Abstract
The renin-angiotensin system (RAS) contributes to vascular disease with multiple cardiovascular risk factors including hypertension. As a major effector within the RAS, angiotensin II (Ang II) activates diverse signaling mechanisms that affect vascular biology. Despite the impact of such vascular pathophysiology, our understanding of the effects of Ang II in relation to the function of endothelial cells is incomplete. Because genetic background and biological sex can be determinants of vascular disease, we performed studies examining the direct effects of Ang II using carotid arteries from male and female mice on two genetic backgrounds, C57BL/6J and FVB/NJ. Although FVB/NJ mice are much less susceptible to atherosclerosis than C57BL/6J, the effects of Ang II on endothelial cells in FVB/NJ are poorly defined. Overnight incubation of isolated arteries with Ang II (10 nmol/L), impaired endothelial function in both strains and sexes by approximately one-half (p < 0.05). To examine the potential mechanistic contribution of Rho kinase (ROCK), we treated arteries with SLX-2119, an inhibitor with high selectivity for ROCK2. In both male and female mice of both strains, SLX-2119 largely restored endothelial function to normal, compared to vessels treated with vehicle. Thus, Ang II-induced endothelial dysfunction was observed in both FVB/NJ and C57BL/6J mice. This effect was sex-independent. In all groups, effects of Ang II were reversed by inhibition of ROCK2 with SLX-2119. These studies provide the first evidence that ROCK2 may be a key contributor to Ang II-induced endothelial dysfunction in both sexes and in mouse strains that differ in relation to other major aspects of vascular disease.
Details
- Title: Subtitle
- Angiotensin II‐induced endothelial dysfunction: Impact of sex, genetic background, and rho kinase
- Creators
- Dale A. Kinzenbaw - University of IowaLucy Langmack - Roy J. and Lucille A. Carver College of MedicineFrank M. Faraci - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Physiological reports, Vol.10(11), pp.e15336-n/a
- DOI
- 10.14814/phy2.15336
- PMID
- 35681278
- PMCID
- PMC9184751
- NLM abbreviation
- Physiol Rep
- eISSN
- 2051-817X
- Grant note
- DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: NS‐096465, NS‐108409
- Language
- English
- Date published
- 06/2022
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984303748602771
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