Platelet Cyclic GMP Levels Are Reduced in Patients with Primary Aldosteronism

Carla Sala; Marta Rescaldani; Elisa Gherbesi; Gianni Bolla; Cesare Cuspidi; Massimiliano Ruscica; Stefano Carugo

doi:10.3390/jcm12227081

Platelet Cyclic GMP Levels Are Reduced in Patients with Primary Aldosteronism

J Clin Med. 2023 Nov 14;12(22):7081. doi: 10.3390/jcm12227081.

Authors

Carla Sala^{1

2}, Marta Rescaldani³, Elisa Gherbesi¹, Gianni Bolla^{1

2}, Cesare Cuspidi⁴, Massimiliano Ruscica^{1

5}, Stefano Carugo^{1

2}

Affiliations

¹ Department of Cardio-Thoracic-Vascular Diseases, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
² Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.
³ Cardiovascular Department, Association Socio Sanitary Territorial Santi Paolo e Carlo, 20153 Milan, Italy.
⁴ Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy.
⁵ Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", University of Milan, 20122 Milan, Italy.

Abstract

Background and aim: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: cyclic guanosine-3′,5′-monophosphate; essential hypertension; nitric oxide; primary aldosteronism.

Grants and funding

This work was partially supported by the Italian Ministry of Health, Ricerca Corrente 2023 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico to S.C. and by the Italian Ministry of University and Research (grant number 2022ZPS49L) to M.R. and S.C. and by the European Union—Next Generation EU, Italian National Recovery and Resilience Plan, (Mission 4, Component 2, Investment 1.5 “Innovation Ecosystems”), project MUSA to M.R. and S.C.