Role of 20-Hydroxyeicosatetraenoic Acid in Mediating Hypertension in Response to Chronic Renal Medullary Endothelin Type B Receptor Blockade
| Autor: | Eric M. George, Marietta Arany, Joey P. Granger, Joshua S. Speed, Kathy Cockrell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Anatomy and Physiology Time Factors Medullary cavity Endothelin B Receptor Antagonists lcsh:Medicine Blood Pressure 030204 cardiovascular system & hematology Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Molecular Cell Biology Hydroxyeicosatetraenoic Acids medicine Renal medulla Animals Membrane Receptor Signaling Salt intake Sodium Chloride Dietary Receptor lcsh:Science Biology 030304 developmental biology 0303 health sciences Renal Physiology Kidney Medulla Multidisciplinary Chemistry lcsh:R Renal System 20-Hydroxyeicosatetraenoic acid Blockade Rats medicine.anatomical_structure Endocrinology Nephrology Hypertension Medicine lcsh:Q Endothelin receptor Research Article Signal Transduction |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 10, p e26063 (2011) |
| ISSN: | 1932-6203 |
| Popis: | Background The renal medullary endothelin (ET-1) system plays an important role in the control of sodium excretion and arterial pressure (AP) through the activation of renal medullary ET-B receptors. We have previously shown that blockade of endothelin type B receptors (ET-B) leads to salt-sensitive hypertension through mechanisms that are not fully understood. One possible mechanism is through a reduction in renal medullary production of 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a metabolite of arachidonic acid, has natriuretic properties similar to ET-B activation. While these findings suggest a possible interaction between ET-B receptor activation and 20-HETE production, it is unknown whether blockade of medullary ET-B receptors in rats maintained on a high sodium intake leads to reductions in 20-HETE production. Methodology/Principal Findings The effect of increasing sodium intake from low (NS = .8%) to high (HS = 8%) on renal medullary production of 20-HETE in the presence and absence of renal medullary ET-B receptor antagonism was examined. Renal medullary blockade of ET-B receptors resulted in salt sensitive hypertension. In control rats, blood pressure rose from 112.8±2.4 mmHg (NS) to 120.7±9.3 mmHg (HS). In contrast, when treated with an ET-B receptor blocker, blood pressure 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 NS vs. 14.3±3.7 pg/mg in HS), an effect that was completely abolished by renal medullary ET-B receptor blockade (4.9±.8 for NS and 4.5±.6 pg/mg for HS). Finally, the hypertensive response to intramedullary ET-B receptor blockade was blunted in rats pretreated with a specific 20-HETE synthesis inhibitor. Conclusion These data suggest that increases in renal medullary production of 20-HETE associated with elevating salt intake may be, in part, due to ET-B receptor activation within the renal medulla. |
| Databáze: | OpenAIRE |
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