Sodium and angiotensin in hypertension induced by long-term nitric oxide blockade.
The influence of dietary sodium restriction and angiotensin II blockade on hypertension induced by a 25-day period of administration of the inhibitor of nitric oxide synthesis NG-nitro-L-arginine-methyl ester (10 mg/kg twice daily by gavage) was assessed in Wistar rats fed a normal or low sodium diet. In addition, the angiotensin II receptor blocker losartan (30 mg/kg once daily by gavage) was administered before and during NG-nitro-L-arginine-methyl ester in rats fed the normal sodium diet. At the end of the studies, conscious systolic arterial pressure increased similarly in NG-nitro-L-arginine-methyl ester-treated groups maintained on normal or low sodium intake. Moreover, a 25% reduction in cardiac output due to a decrease in stroke volume was observed in both groups. A slight but significant cardiac hypertrophic response was observed in hypertensive rats irrespective of sodium intake. At the completion of studies, plasma renin activity was similar to corresponding controls in the hypertensive groups on normal or low sodium intake. Losartan totally prevented the development of hypertension as well as the decrease in stroke volume and cardiac hypertrophy associated with NG-nitro-L-arginine-methyl ester treatment in rats on normal sodium intake. In conclusion, hypertension resulting from long-term blockade of nitric oxide synthesis was not affected by dietary sodium restriction. A crucial role for the renin-angiotensin system was demonstrated in this new model of hypertension.
Groupe Rein et Hypertension, Centre Hospitalier Universitaire, Montpellier, France.
B
B
Jover
A
A
Herizi
F
F
Ventre
M
M
Dupont
A
A
Mimran
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives*; D001713:Biphenyl Compounds / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D004573:Electrolytes / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
D001713:Biphenyl Compounds; D004573:Electrolytes; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester