Effects of high‐ and low‐dose aspirin on adaptive immunity and hypertension in the stroke‐prone spontaneously hypertensive rat. Issue 1 (29th August 2018)

• Record Type: Journal Article
• Authors: Khan, Shanzana I.; Shihata, Waled A.; Andrews, Karen L.; Lee, Man K. S.; Moore, Xiao-Lei; Jefferis, Ann-Maree; Vinh, Antony; Gaspari, Tracey; Dragoljevic, Dragana; Jennings, Garry L.; Murphy, Andrew J.; Chin-Dusting, Jaye P. F.
• Is Part Of: FASEB journal. Volume 33:Issue 1(2019)
• Page Start: 1510
• Page End: 1521
• Publication Date: 2018-08-29
• Subjects: cyclooxygenase -- cardiac hypertrophy -- vascular function -- renal fibrosis -- prostanoids; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201701498RR
• Languages: English
• ISSNs: 0892-6638

Abstract

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.—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. Effects of high‐ and low‐dose aspirin on adaptive immunity and hypertension in the stroke‐prone spontaneously hypertensive rat. FASEB J. 33, 1510–1521 (2019). www.fasebj.org