Low-renin hypertension with relative aldosterone excess is associated with impaired NO-mediated vasodilation.

Recent studies suggest that hypertension associated with low renin status and hyperaldosteronism is associated with increased risk for end-organ damage and cardiovascular events compared with other forms of hypertension. Additionally, experimental studies have demonstrated impaired nitric oxide-mediated bioactivity in these states. To investigate the relation between renin/aldosterone status and resistance vessel function, we examined plasma renin activity, serum aldosterone level, and forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilators sodium nitroprusside and verapamil using venous occlusion plethysmography in 130 volunteers (43 hypertensive, 87 normotensive). Low renin status was associated with impaired responses to methacholine and nitroprusside in patients with hypertension. Peak methacholine response was 8.7+/-5.6 mL/min per dL in the lowest renin quartile (0.1 to 0.3 ng/mL per hour) versus 14.3+/-7.3 mL/min per dL in the highest 3 renin quartiles combined (0.4 to 4.6 ng/mL per hour; P<0.001). Peak nitroprusside response was 5.6+/-2.3 mL/min per dL in the lowest renin quartile versus 13.3+/-4.1 mL/min per dL in the highest 3 renin quartiles combined (P<0.001). Blood pressure and other clinical characteristics were similar in all 4 quartiles. Vasodilator responses to verapamil did not relate to renin activity. Methacholine and nitroprusside responses did not relate to renin status in normotensive controls (P=0.34). Importantly, hypertensive patients with a high aldosterone/renin ratio also had impaired responses to methacholine. This study demonstrates that low-renin hypertension is associated with marked impairment of nitric oxide-mediated vasodilation of resistance vessels in the forearm vasculature of humans. This impairment could contribute to adverse outcomes in patients with low-renin hypertension and relative aldosterone excess.