1. No evidence for brain renin-angiotensin system activation during DOCA-salt hypertension
- Author
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Liwei Ren, Estrellita Uijl, Don Foster, Stephen Huang, Katrina M Mirabito Colafella, Jae B. Kim, Lauren Melton, Ingrid M. Garrelds, Richard van Veghel, Marko Poglitsch, A.H. Jan Danser, Ewout J. Hoorn, Oliver Domenig, Ivan Zlatev, and Internal Medicine
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Angiotensinogen ,Rats, Sprague-Dawley ,Renin-Angiotensin System ,Desoxycorticosterone Acetate ,chemistry.chemical_compound ,Mineralocorticoid receptor ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,cardiovascular diseases ,Sodium Chloride, Dietary ,Chemistry ,urogenital system ,Angiotensin II ,Brain ,General Medicine ,Receptor antagonist ,medicine.disease ,Hyperaldosteronism ,Blood pressure ,Endocrinology ,Valsartan ,Hypertension ,Spironolactone ,hormones, hormone substitutes, and hormone antagonists ,Brain Stem ,medicine.drug ,circulatory and respiratory physiology - Abstract
Brain renin–angiotensin system (RAS) activation is thought to mediate deoxycorticosterone acetate (DOCA)-salt hypertension, an animal model for human primary hyperaldosteronism. Here, we determined whether brainstem angiotensin II is generated from locally synthesized angiotensinogen and mediates DOCA-salt hypertension. To this end, chronic DOCA-salt-hypertensive rats were treated with liver-directed siRNA targeted to angiotensinogen, the angiotensin II type 1 receptor antagonist valsartan, or the mineralocorticoid receptor antagonist spironolactone (n = 6–8/group). We quantified circulating angiotensinogen and renin by enzyme-kinetic assay, tissue angiotensinogen by Western blotting, and angiotensin metabolites by LC-MS/MS. In rats without DOCA-salt, circulating angiotensin II was detected in all rats, whereas brainstem angiotensin II was detected in 5 out of 7 rats. DOCA-salt increased mean arterial pressure by 19 ± 1 mmHg and suppressed circulating renin and angiotensin II by >90%, while brainstem angiotensin II became undetectable in 5 out of 7 rats (
- Published
- 2021