Reduced Platelet cGMP Levels in Primary Aldosteronism

Geeralom Etikiresarinika^*
*Correspondence: Geeralom Etikiresarinika, Department of Clinical Sciences and Community Health, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea, Email:

Introduction

Primary Aldosteronism (PA) is a common cause of secondary hypertension characterized by excessive production of aldosterone by the adrenal glands. While aldosterone is primarily known for its role in sodium and potassium homeostasis, emerging evidence suggests that it may also influence platelet function through modulation of cyclic Guanosine Monophosphate (cGMP) levels. Reduced platelet cGMP levels have been observed in various cardiovascular conditions, including hypertension, heart failure and atherosclerosis. However, the relationship between aldosterone excess and platelet cGMP levels in patients with primary aldosteronism remains poorly understood. This paper provides a comprehensive overview of the association between reduced platelet cGMP levels and primary aldosteronism, drawing upon existing literature and recent research findings. The introduction section sets the stage by outlining the pathophysiology of primary aldosteronism, the role of aldosterone in platelet function and the potential implications of reduced platelet cGMP levels in this population. Subsequent sections will delve into the methodology, results and clinical implications of studies investigating platelet cGMP levels in primary aldosteronism, culminating in a thorough conclusion that synthesizes key findings and identifies avenues for future research [1].

Description

Primary Aldosteronism (PA) is characterized by autonomous aldosterone secretion from the adrenal glands, leading to sodium retention, potassium excretion and hypertension. Aldosterone exerts its effects through binding to mineralocorticoid receptors in the kidney, promoting sodium reabsorption and potassium secretion. However, emerging evidence suggests that aldosterone may also have non-renal effects, including modulation of vascular tone, inflammation and platelet function. Platelets, small cell fragments involved in hemostasis and thrombosis, express mineralocorticoid receptors and are sensitive to aldosterone stimulation. Cyclic Guanosine Monophosphate (cGMP) is a key signaling molecule involved in platelet activation and aggregation. Reduced platelet cGMP levels have been observed in various cardiovascular conditions, including hypertension, heart failure and atherosclerosis. In animal models, aldosterone has been shown to decrease platelet cGMP levels by inhibiting soluble guanylate cyclase, the enzyme responsible for cGMP synthesis. However, the clinical significance of reduced platelet cGMP levels in patients with primary aldosteronism remains unclear [2,3].

Several studies have investigated platelet cGMP levels in patients with primary aldosteronism, aiming to elucidate the relationship between aldosterone excess and platelet function. Early studies reported conflicting results, with some demonstrating decreased platelet cGMP levels in patients with primary aldosteronism compared to essential hypertension or normotensive controls, while others found no significant differences. More recent studies have sought to clarify these discrepancies by employing more rigorous methodology and larger sample sizes. Studies investigating the association between reduced platelet cGMP levels and primary aldosteronism employ various methodologies to assess platelet function and aldosterone status in study participants. Enzyme immunoassays and radioimmunoassays are commonly used to measure platelet cGMP levels, with samples typically obtained from peripheral blood draws. In addition to platelet cGMP levels, researchers may also assess other markers of platelet activation and aggregation, such as P-selectin expression and aggregation assays [4].

Aldosterone status is typically assessed through measurement of Plasma Aldosterone Concentration (PAC) and Plasma Renin Activity (PRA). The Aldosterone-To-Renin Ratio (ARR) is commonly used as a screening test for primary aldosteronism, with an elevated ARR suggestive of aldosterone excess. Confirmatory testing may include saline infusion tests, oral sodium loading tests, or captopril challenge tests to further characterize aldosterone production and suppressibility. Study participants may include patients with confirmed primary aldosteronism, essential hypertension, normotensive controls and/or other cardiovascular conditions. Demographic and clinical data, including age, sex, blood pressure measurements, medication use, comorbidities and laboratory values, are collected and analyzed to assess potential confounding factors. The findings of studies investigating platelet cGMP levels in primary aldosteronism have important clinical implications for risk stratification and therapeutic management. Reduced platelet cGMP levels may serve as a biomarker of cardiovascular risk in patients with primary aldosteronism, identifying individuals at increased risk of thrombotic events, myocardial infarction and stroke. Incorporating platelet function testing into routine clinical practice may help identify high-risk patients who may benefit from more aggressive antithrombotic therapy or closer monitoring. Furthermore, the association between aldosterone excess and platelet dysfunction suggests potential therapeutic targets for intervention. Pharmacological agents that modulate aldosterone signaling pathways, such as mineralocorticoid receptor antagonists or aldosterone synthase inhibitors, may offer novel approaches for reducing cardiovascular risk in patients with primary aldosteronism. Future clinical trials are needed to evaluate the efficacy and safety of these agents in improving platelet function and reducing cardiovascular events in this population [5].

Conclusion

In conclusion, reduced platelet cGMP levels have emerged as a potential biomarker of cardiovascular risk in patients with primary aldosteronism. While the precise mechanisms underlying this association remain incompletely understood, accumulating evidence suggests that aldosterone excess may contribute to platelet dysfunction through modulation of cGMP signaling pathways. Future research efforts should focus on elucidating the pathophysiological mechanisms linking aldosterone excess to reduced platelet cGMP levels, as well as exploring the clinical implications of these findings for risk stratification and therapeutic intervention in patients with primary aldosteronism. By advancing our understanding of the complex interplay between aldosterone, platelet function and cardiovascular risk, we can ultimately improve the management and outcomes of patients with this common and underdiagnosed form of secondary hypertension.

Acknowledgment

None.

Conflict of Interest

No conflict of interest.

References

1. Buffolo, Fabrizio, Martina Tetti, Paolo Mulatero and Silvia Monticone. "Aldosterone as a mediator of cardiovascular damage." Hypertension 79 (2022): 1899-1911.

Google Scholar, Crossref, Indexed at

2. Schiffrin, Ernesto L. "Effects of aldosterone on the vasculature." Hypertension 47 (2006): 312-318.

Google Scholar, Crossref, Indexed at

3. Jia, Guanghong, Javad Habibi, Annayya R. Aroor and Michael A. Hill, et al. "Epithelial sodium channel in aldosterone-induced endothelium stiffness and aortic dysfunction." Hypertension 72 (2018): 731-738.

Google Scholar, Crossref, Indexed at

4. Alexander, Yvonne, Elena Osto, Arno Schmidt-Trucksäss and Michael Shechter, et al. "Endothelial function in cardiovascular medicine: A consensus paper of the European society of cardiology working groups on atherosclerosis and vascular biology, aorta and peripheral vascular diseases, coronary pathophysiology and microcirculation, and thrombosis." Cardiovasc Res 117 (2021): 29-42.

Google Scholar, Crossref, Indexed at

5. Nagata, Daisuke, Masao Takahashi, Kuniko Sawai and Tetsuya Tagami, et al. "Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity." Hypertension 48 (2006): 165-171.

Google Scholar, Crossref, Indexed at