Nuclear Receptors in Hemodynamics and Blood Pressure Control

Unlike surface receptors that elicit biological responses through second messenger signaling, nuclear receptors (NRs) are a large family of transcription factors that directly binds to genomic DNA and regulate the expression of target genes. NRs typically consist of 1) a ligand binding domain (LBD) that binds ligands with high affinity, 2) a DNA binding domain (DBD) and a hinge domain that together interact with hormone response elements (HREs) at DNA transcription regulation sites, and 3) a transactivation domain that supports NR dimerization. The LBD and DBD are signature structures of NRs across mouse, rat, and humans. While some NRs may bind DNA as a monomer (Type IV), they generally function as homodimers (Type I & III) or heterodimers (Type II). Ligand binding triggers a cascade of molecular events that invariably lead to the assembly of NR/DNA/transcription coregulator complexes that either activate or suppress transcription of target genes.



In response to endogenous or exogenous ligands such as lipids, vitamins, and hormones, NRs regulate a wide range of biological processes, including growth and development, metabolism, homeostasis, and reproduction. The natural NR ligands are small hydrophobic molecules, making it easy to design structural analogues as pharmacological modulators of NRs. Numerous synthetic agonists, antagonists, and selective receptor modulators have been developed for research and clinical use. In the cardiovascular system, NRs play key roles in control of hemodynamics and blood pressure. Steroid hormone receptors and peroxisome proliferator-activated receptors (PPARs) are well established regulators of sympathetic outflow, cardiac output, vascular function, renal water/electrolyte transport, inflammation, and other physiological responses. The aim of this collection is to highlight new insights into the physiological functions of NRs in controlling hemodynamics and blood pressure.