Aldosterone receptor antagonism reduces urinary C-reactive protein excretion in angiotensin II–infused, hypertensive rats

Elevated C-reactive protein (CRP) may contribute to elevated arterial pressure in angiotensin (Ang) II–dependent hypertension. However, the in vivo effects of Ang II and of mineralocorticoid receptor (MR) antagonism on CRP during Ang II–dependent hypertension have not been examined. In addition, urinary CRP excretion as a method to monitor the progression of Ang II–induced inflammation has not been evaluated. Urine samples were collected from 3 groups (n = 10/group) of rats: normotensive control, Ang II–infused (60 ng/minute), and Ang II + eplerenone (epl; 25 mg/day). A diet containing epl (0.1%) was provided after 1 week of Ang II infusion. After 28 days, Ang II increased systolic blood pressure (SBP) from 136 ± 5 to 207 ± 8 mm Hg; this response in SBP was not altered after MR antagonism (215 ± 6 mm Hg). Ang II infusion increased plasma CRP from 14 ± 2 to 26 ± 3 μg/mL and increased urinary immunoreactive CRP (irCRP) excretion nearly 8-fold (143 ± 26 vs. 1102 ± 115 ng/day). Treatment with eplerenone reduced plasma CRP by 25% and urinary irCRP by 34% in Ang II–infused rats, suggesting that aldosterone contributes to the CRP-associated inflammatory response in Ang II–dependent hypertension. The increase in SBP preceded the increase in irCRP excretion by at least 4 days, suggesting that CRP does not significantly contribute to increased arterial BP in Ang II–dependent hypertension. The blockade of MR reduced plasma CRP and urinary irCRP excretion, demonstrating the contribution of aldosterone to the Ang II–induced generation of CRP. Furthermore, urinary CRP may serve as a noninvasive index for monitoring cardiovascular inflammation during hypertension.