Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension

Q: What is the clinical evidence from this study?

Study design: Review. Population: Hypertension. Intervention: Purinergic receptor antagonists.

Q: What does this research mean for the field?

Activation of renal purinergic receptors by elevated ATP contributes to the development and maintenance of hypertension, suggesting purinergic antagonists as a potential complementary treatment. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Rocío Bautista‐Pérez; Martha Franco

doi:10.3390/ph17081060

August 13, 2024PharmaceuticalsOpen Access

Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension

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Key result

Purinergic receptor antagonists may curb CKD progression in hypertension by reducing inflammation and vasoconstriction.

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Why the study?

Despite current treatments, blood pressure remains difficult to control and causes cardiovascular complications, necessitating new approaches such as understanding purinergic receptor involvement in hypertension.

Do purinergic receptor antagonists prevent the progression of renal damage in hypertension?

Key Points

To review the pathological contributions of renal purinergic receptors and elevated interstitial ATP in the development of hypertension and evaluate purinergic antagonists as therapeutic options.
Synthesized literature on the distribution and actions of P2X and P2Y purinergic receptor families across distinct nephron segments and renal vascular beds.
Examined mechanistic links between extracellular ATP release, tubulointerstitial inflammatory infiltration, angiotensin II interactions, and impaired pressure natriuresis.
Elevated renal interstitial ATP activates purinergic receptors, impairing pressure natriuresis, autoregulation of renal blood flow, and tubuloglomerular feedback, which decreases urinary sodium excretion.
Interactions between angiotensin II and purinergic signaling stimulate renal vasoconstriction, hypoxia, oxidative stress, and inflammatory cytokine release, driving tubulointerstitial damage.
Evidence indicates targeting overexpressed purinergic receptors (such as P2X1 and P2X7) with receptor antagonists represents a viable complementary strategy to protect renal function in hypertension.

Structured PICO

Do purinergic receptor antagonists prevent the progression of renal damage in hypertension?

P

Population

Hypertensive patients and experimental models of hypertension

I

Intervention

Purinergic receptor antagonists (P2X and P2Y antagonists)

Purinergic receptor antagonists represent a potential novel therapeutic target for preventing renal damage in salt-sensitive and uncontrolled hypertension.

Limitations

Identifying the correct moment to initiate therapy during hypertension
Selecting markers to evaluate the effects of the therapy

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Implication

Hypothesis-generating for purinergic antagonism in hypertensive CKD prevention; randomized trials needed before clinical consideration.

Abstract

The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as chronic renal failure, which is frequently observed in hypertensive patients. Therefore, new approaches that may improve the control of arterial blood pressure should be considered to prevent serious cardiovascular disorders. The contribution of purinergic receptors has been acknowledged in the pathophysiology of hypertension; this review describes the participation of these receptors in the alteration of kidney function in hypertension. Elevated interstitial ATP concentrations are essential for the activation of renal purinergic receptors; this becomes a fundamental pathway that leads to the development and maintenance of hypertension. High ATP levels modify essential mechanisms implicated in the long-term control of blood pressure, such as pressure natriuresis, the autoregulation of the glomerular filtration rate and renal blood flow, and tubuloglomerular feedback responses. Any alteration in these mechanisms decreases sodium excretion. ATP stimulates the release of vasoactive substances, causes renal function to decline, and induces tubulointerstitial damage. At the same time, a deleterious interaction involving angiotensin II and purinergic receptors leads to the deterioration of renal function.

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Cite This Study

Bautista‐Pérez et al. (2024) conducted a review in Hypertension. Purinergic receptor antagonists was evaluated. Purinergic receptor antagonists may prevent the progression of renal damage to chronic kidney disease in hypertensive patients by reducing ATP-mediated tubulointerstitial inflammation and vasoconstriction.

synapsesocial.com/papers/6a1fd928a4cb436d84ba5167 https://doi.org/10.3390/ph17081060

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Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension

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Key Points

Structured PICO

Limitations

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Implication

Abstract

Discussion

Cite This Study

Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension

Figures

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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