| First Author | Ivy JR | Year | 2018 |
| Journal | Front Physiol | Volume | 9 |
| Pages | 848 | PubMed ID | 30038578 |
| Mgi Jnum | J:275896 | Mgi Id | MGI:6307211 |
| Doi | 10.3389/fphys.2018.00848 | Citation | Ivy JR, et al. (2018) Renal and Blood Pressure Response to a High-Salt Diet in Mice With Reduced Global Expression of the Glucocorticoid Receptor. Front Physiol 9:848 |
| abstractText | Salt-sensitive hypertension is common in glucocorticoid excess. Glucocorticoid resistance also presents with hypercortisolemia and hypertension but the relationship between salt intake and blood pressure (BP) is not well defined. GR(betageo/+) mice have global glucocorticoid receptor (GR) haploinsufficiency and increased BP. Here we examined the effect of high salt diet on BP, salt excretion and renal blood flow in GR(betageo/+)mice. Basal BP was approximately 10 mmHg higher in male GR(betageo/+) mice than in GR(+/+) littermates. This modest increase was amplified by approximately 10 mmHg following a high-salt diet in GR(betageo/+) mice. High salt reduced urinary aldosterone excretion but increased renal mineralocorticoid receptor expression in both genotypes. Corticosterone, and to a lesser extent deoxycorticosterone, excretion was increased in GR(betageo/+) mice following a high-salt challenge, consistent with enhanced 24 h production. GR(+/+) mice increased fractional sodium excretion and reduced renal vascular resistance during the high salt challenge, retaining neutral sodium balance. In contrast, sodium excretion and renal vascular resistance did not adapt to high salt in GR(betageo/+) mice, resulting in transient sodium retention and sustained hypertension. With high-salt diet, Slc12a3 and Scnn1a mRNAs were higher in GR(betageo/+) than controls, and this was reflected in an exaggerated natriuretic response to thiazide and benzamil, inhibitors of NCC and ENaC, respectively. Reduction in GR expression causes salt-sensitivity and an adaptive failure of the renal vasculature and tubule, most likely reflecting sustained mineralocorticoid receptor activation. This provides a mechanistic basis to understand the hypertension associated with loss-of-function polymorphisms in GR in the context of habitually high salt intake. |
