Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat

Shanzana I. Khan, Waled A. Shihata, Karen L. Andrews, Man K. S. Lee, Xiao-Lei Moore, Ann-Maree Jefferis, Antony Vinh, Tracey Gaspari, Dragana Dragoljevic, Garry L. Jennings, Andrew J. Murphy, Jaye P. F. Chin-Dusting

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4 Citations (Scopus)

Abstract

Despite its well-known antithrombotic properties, the effect of aspirin on blood pressure (BP) and hypertension pathology is unclear. The hugely varying doses used clinically have contributed to this confusion, with high-dose aspirin still commonly used due to concerns about the efficacy of low-dose aspirin. Because prostaglandins have been shown to both promote and inhibit T-cell activation, we also explored the immunomodulatory properties of aspirin in hypertension. Although the common preclinical high dose of 100 mg/kg/d improved vascular dysfunction and cardiac hypertrophy, this effect was accompanied by indices of elevated adaptive immunity, renal T-cell infiltration, renal fibrosis, and BP elevation in stroke-prone spontaneously hypertensive rats and in angiotensin II-induced hypertensive mice. The cardioprotective effects of aspirin were conserved with a lower dose (10 mg/kg/d) while circumventing heightened adaptive immunity and elevated BP. We also show that low-dose aspirin improves renal fibrosis. Differential inhibition of the COX-2 isoform may underlie the disparate effects of the 2 doses. Our results demonstrate the efficacy of low-dose aspirin in treating a vast array of cardiovascular parameters and suggest modulation of adaptive immunity as a novel mechanism underlying adverse cardiovascular profiles associated with COX-2 inhibitors. Clinical studies should identify the dose of aspirin that achieves maximal cardioprotection with a new awareness that higher doses of aspirin could trigger undesired autoimmunity in hypertensive individuals. This work also warrants an evaluation of high-dose aspirin and COX-2 inhibitor therapy in sufferers of inflammatory conditions who are already at increased risk for cardiovascular disease.

Original languageEnglish
Pages (from-to)1510-1521
Number of pages12
JournalThe FASEB Journal
Volume33
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Cardiac hypertrophy
  • Cyclooxygenase
  • Prostanoids
  • Renal fibrosis
  • Vascular function

Cite this

Khan, S. I., Shihata, W. A., Andrews, K. L., Lee, M. K. S., Moore, X-L., Jefferis, A-M., Vinh, A., Gaspari, T., Dragoljevic, D., Jennings, G. L., Murphy, A. J., & Chin-Dusting, J. P. F. (2019). Effects of high- and low-dose aspirin on adaptive immunity and hypertension in the stroke-prone spontaneously hypertensive rat. The FASEB Journal, 33(1), 1510-1521. https://doi.org/10.1096/fj.201701498RR