Purinoceptor: a novel target for hypertension

Abstract

Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension through the sympathetic nerve system, neurons in the brain stem, carotid body, endothelium, immune system, renin-angiotensin system, sodium excretion, epithelial sodium channel activity (ENaC), and renal autoregulation. Under hypertension, adenosine triphosphate (ATP) is released as a cotransmitter from the sympathetic nerve. It mediates vascular tone mainly through P2X1R activation on smooth muscle cells and activation of P2X4R and P2YR on endothelial cells and also via interaction with other purinoceptors, showing dual effects. P2Y1R is linked to neurogenic hypertension. P2X7R and P2Y11R are potential targets for immune-related hypertension. P2X3R located on the carotid body is the most promising novel therapeutic target for hypertension. A1R, A2AR, A2BR, and P2X7R are all related to renal autoregulation, which contribute to both renal damage and hypertension. The main focus is on the evidence addressing the involvement of purinoceptors in hypertension and therapeutic interventions.

Pharmacological Nature of the Purinergic P2Y Receptor Subtypes That Participate in the Blood Pressure Changes Produced by ADPβS in Rats

“…In keeping with this suggestion, other studies have recently revealed that endothelial P2Y 1 receptors are critical in mediating nitric oxide-dependent vasorelaxation [44] and in processes essential for the regeneration of damaged endothelium [45]. This knowledge has stimulated increased interest in considering the P2Y 1 receptor as a potential therapeutic target in the treatment of hypertension [46].…”

Updates in the management of hypertension

“…Ultrasound and radiofrequency RDN showed remarkable BP lowering in off-medicated uncontrolled hypertension patients by 6.3 and 5 mmHg, respectively 9 , 68 . Purinoceptor-mediated effects and purines such as adenosine tri phosphate (ATP) has been observed to increase BP making it a novel target for hypertension treatment that might have an impact on the regulation patterns 69 .…”

Pathogenic Mechanisms of Pulmonary Arterial Hypertension

“…Since 1972, numerous studies have demonstrated that adenosine triphosphate acts as an extracellular signaling molecule that controls blood pressure. 97 In fact, cells including erythrocytes, ECs, and immune cells can produce nucleotides (adenosine triphosphate, adenosine diphosphate, uridine triphosphate, uridine diphosphate) or nucleosides (adenosine) that bind to purinergic receptors for their biological functions. These purinergic receptors contain 2 subfamilies, namely, P1R and P2R.…”