A New Approach for Treatment of Hypertension: Modifying D1 Dopamine Receptor Function

Chunyu      Zeng; Robin   A.   Felder; Pedro   A.   Jose

Abstract

Essential hypertension is a major factor for myocardial infarction, heart failure and kidney failure. Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and vasodilatation directly or indirectly with other hormones and humoral factors, such as reactive oxygen species and the renin-angiotensin system. Dopamine receptors are classified into five subtypes based on their structure and pharmacology. Among those dopamine receptor subtypes, D1 receptor is the most important one, during conditions of moderate sodium intake, more than 50% of renal sodium excretion is regulated by D1-like receptors. Decreased renal dopamine production and/or impaired D1 receptor function have been reported in hypertension. Disruption of D1 receptor results in hypertension. In this paper, we review the mechanisms by which hypertension develops when D1 receptor function is perturbed. We also discuss possible new approaches developing anti-hypertensive medicine by increasing renal dopamine production, enhancing D1 receptor function, or modifying its interactions with other blood pressure-regulating systems.

Keywords: Essential hypertension, D1 dopamine receptor, G protein-coupled receptor kinase type 4, protein phosphotase 2A, endocytosis, desensitization, sodium excretion, vasorelaxation