Chronic inhibition of medullary ET‐B receptors attenuates elevations in 20‐HETE associated with increasing sodium intake

• Published in: The FASEB journal Vol. 25; no. S1; p. 1079.10
• Main Authors: Speed, Joshua, Arany, Marietta, Cockrell, Kathy, Purser, Christine, Baker, Rodney, Roman, Richard, Granger, Joey
• Format: Journal Article
• Language: English
• Published: Federation of American Societies for Experimental Biology 01-04-2011
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.25.1_supplement.1079.10

Renal medullary endothelin (ET‐1) plays an important role in the control arterial pressure (AP) through the activation of ET‐B receptors. We have shown that intramedullary (IM) blockade of ET‐B receptors leads to salt sensitive hypertension through mechanisms that have yet to be fully elucidated. One possibility is through a reduction in 20‐HETE, which is elevated in response to a high salt intake. In addition, IM blockade of 20‐HETE causes salt sensitive hypertension. While these data suggest a possible interaction between medullary ET‐1 and 20‐HETE, it is unknown whether blockade of medullary ET‐B receptors leads to a decrease in 20‐HETE production. Therefore, we examined the effect of high (HS=8%) and low (LS=.8%) salt diet on renal medullary production of 20‐HETE in the presence and absence of renal medullary ET‐B receptor antagonism. In control rats, AP rose from 112.8 ± 2.4 mmHg (NS) to 120.7 ± 9.3 mmHg (HS). In contrast, when treated with an ET‐B blocker, AP was significantly elevated from 123.7 ± 3.2 (NS) to 164.2 ± 7.1 (HS). Furthermore, increasing sodium intake was associated with elevated medullary 20‐HETE (5.6 ± .8 in LS vs. 14.3 ± 3.7 pg/mg in HS), an effect that was completely abolished by ET‐B blockade (4.9 ± .8 for NS and 4.5 ± .6 pg/mg for HS). These data suggest that hypertension in response to ET‐B blockade is due at least in part through a reduction in the renal medullary production of 20‐HETE.