Platelet Cyclic GMP Levels Are Reduced in Patients with Primary Aldosteronism

Nitric oxide inhibits platelet aggregation by increasing the second messenger cyclic guanosine-3',5'-monophosphate (cGMP) through the activation of soluble guanylyl cyclase in target cells. Within this context, the oxidative stress associated with the aldosterone excess impairs the nitric oxide availability. Thus, the aim of the present study was to assess the impact of chronic aldosterone excess on the platelet nitric oxide/cGMP pathway in humans.

The levels of cGMP were evaluated in platelets of male patients, 12 with primary aldosteronism (PA) and 32 with uncomplicated essential hypertension (EH), matched for age and blood pressure (BP) values.

PA and EH patients were 52.8 ± 3 years old and 51.6 ± 1.6 years old, respectively. Systolic and diastolic BP were 158 ± 5.0 mmHg and 105.9 ± 2.3 mmHg in PA and did not differ compared to EH patients (156.6 ± 2.4 mmHg and 104.7 ± 1.2 mmHg). Mean aldosterone levels were significantly higher in PA (25.5 ± 8.8 ng/dL) compared toEH (8.11 ± 0.73 ng/dL), whereas potassium was significantly lower in PA (3.52 ± 0.18 mEq/L) compared to EH (4.08 ± 0.04 mEq/L). Aldosterone and potassium were inversely related (r = -0.49, p = 0.0006) in the whole study population (n = 44). Platelet cGMP was significantly lower in PA (5.1 ± 0.36 pM/10⁹ cells) than in EH (7.1 ± 0.53 pM/10⁹ cells), and in the entire study cohort, it was directly related to plasma potassium (r = 0.43, p = 0.0321).

These results show an impairment of nitric oxide/cGMP signaling in platelets of PA patients. This effect is likely related to the potassium-depleting effect of chronic aldosterone excess. Future studies are needed to understand whether the platelet nitric oxide/cGMP system is involved in the atherothrombotic events in these patients.