A new approach for treatment of hypertension: modifying D1 dopamine receptor function.
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, D(1) receptor is the most important one, during conditions of moderate sodium intake, more than 50% of renal sodium excretion is regulated by D(1)-like receptors. Decreased renal dopamine production and/or impaired D(1) receptor function have been reported in hypertension. Disruption of D(1) receptor results in hypertension. In this paper, we review the mechanisms by which hypertension develops when D(1) receptor function is perturbed. We also discuss possible new approaches developing anti-hypertensive medicine by increasing renal dopamine production, enhancing D(1) receptor function, or modifying its interactions with other blood pressure-regulating systems.
Zeng
Chunyu
C
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing City, PR China. cyzeng1@hotmail.com
Felder
Robin A
RA
Jose
Pedro A
PA
D000959:Antihypertensive Agents / Q000494:pharmacology*; D003846:Deoxyepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018818:Fenoldopam / Q000494:pharmacology; D054771:G-Protein-Coupled Receptor Kinase 4; D019204:GTP-Binding Proteins / Q000819:agonists / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000187:drug effects* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; C023487:ibopamine; D017346:Protein Serine-Threonine Kinases; D054771:G-Protein-Coupled Receptor Kinase 4; C517855:GRK4 protein, human; D019204:GTP-Binding Proteins; D018818:Fenoldopam; D003846:Deoxyepinephrine; D004298:Dopamine