Effect of magnesium on mRNA expression and production of endothelin-1 in DOCA-salt hypertensive rats.
The aim of this study was to investigate whether or not the decrease in blood pressure induced by dietary magnesium supplementation in DOCA-salt hypertensive rats is associated with modifications in expression and tissular production of endothelin-1. DOCA-salt treatment increased blood pressure, induced renal and cardiac hypertrophy, and increased endothelin-1 expression and production in the kidney, heart, and aorta. Mg supplementation for 8 weeks lowered blood pressure in DOCA-salt hypertensive rats and prevented hypertrophies and the increase of endothelin-1 expression and production in the heart, aorta, and kidney. Treatment with a receptor ETA antagonist, ABT-627, was used to clarify the relationship between the lowering effect of Mg supplementation on blood pressure and endothelin-1 production. When DOCA-salt rats were treated with ABT-627 for 8 weeks, Mg supplementation failed to lower blood pressure. In conclusion, these findings suggest that the lowering effect of Mg supplementation on blood pressure requires an inhibitory effect on endothelin-1 activity and/or endothelin-1 production in DOCA-salt hypertensive rats.
Berthon
Nathalie
N
Laboratoire Physiologie, Pharmacologie et Nutrition Préventive Expérimentale, UFR Médecine et Pharmacie, Université de Franche-Comté, Besançon, France. nathalie1de@aol.com
Laurant
Pascal
P
Fellmann
Dominique
D
Berthelot
Alain
A
D000818:Animals; D001011:Aorta / Q000378:metabolism; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008277:Magnesium Oxide / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D012333:RNA, Messenger; D008277:Magnesium Oxide; D003900:Desoxycorticosterone; D000077868:Atrasentan