Hypothalamic Paraventricular Nucleus Gαi 2 (Guanine Nucleotide–Binding Protein Alpha Inhibiting Activity Polypeptide 2) Protein–Mediated Neural Control of the Kidney and the Salt Sensitivity of Blood Pressure
| Autor: | Sarah Mahne, Jonathan S. Williams, Crissey L. Pascale, Daniel R. Kapusta, Richard D Wainford, Casey Y. Carmichael, Douglas L. Rosene, Jill T. Kuwabara, J. Thomas Cunningham, Jesse D. Moreira |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Kidney Chemistry Guanine Alpha (ethology) 030204 cardiovascular system & hematology Phenotype Norepinephrine (medication) 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Blood pressure medicine.anatomical_structure Biochemistry Salt sensitivity Internal Medicine medicine Nucleus medicine.drug |
| Zdroj: | Hypertension. 75:1002-1011 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | We have previously reported that in salt-resistant rat phenotypes brain, Gαi 2 (guanine nucleotide–binding protein alpha inhibiting activity polypeptide 2) proteins are required to maintain blood pressure and sodium balance. However, the impact of hypothalamic paraventricular nucleus (PVN) Gαi 2 proteins on the salt sensitivity of blood pressure is unknown. Here, by the bilateral PVN administration of a targeted Gαi 2 oligodeoxynucleotide, we show that PVN-specific Gαi 2 proteins are required to facilitate the full natriuretic response to an acute volume expansion (peak natriuresis [μeq/min] scrambled (SCR) oligodeoxynucleotide 41±3 versus Gαi 2 oligodeoxynucleotide 18±4; P 2 proteins are essential to counter renal nerve-dependent salt-sensitive hypertension (mean arterial pressure [mm Hg] 8% NaCl; SCR oligodeoxynucleotide 128±2 versus Gαi 2 oligodeoxynucleotide 147±3; P 2 signaling pathways, which mediate sympathoinhibition to the blood vessels and kidneys (renal norepinephrine [pg/mg] 8% NaCl; SCR oligodeoxynucleotide 375±39 versus Gαi 2 oligodeoxynucleotide 850±27; P 2 protein downregulation prevented PVN parvocellular neuron activation, assessed by FosB immunohistochemistry, in response to increased dietary salt intake. In our analysis of the UK BioBank data set, it was observed that 2 GNAI2 single nucleotide polymorphism (SNP) (rs2298952, P =0.041; rs4547694, P =0.017) significantly correlate with essential hypertension. Collectively, our data suggest that selective targeting and activation of PVN Gαi 2 proteins is a novel therapeutic approach for the treatment of salt-sensitive hypertension. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|