Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats.
Nitric oxide is a potent endogenous vasodilator that regulates arterial tone. A family of nitric oxide synthases uses L-arginine and L-homoarginine stereospecifically as substrates for nitric oxide production in vivo. By preventing expression of inducible but not constitutive nitric oxide synthases, glucocorticoids differentiate which enzyme in this family is the predominant source of nitric oxide generation in a given situation. We proposed that defective production of nitric oxide produces salt-sensitive hypertension in the Dahl/Rapp rat. Plasma concentrations of L-arginine, citrulline, and ornithine of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats on 8% sodium chloride chow for 1 week did not differ. However, intravenous infusion of L-arginine and L-homoarginine, but not D-arginine, increased urinary excretion of nitrate, the degradation product of nitric oxide, and simultaneously lowered blood pressure in hypertensive SS/Jr rats. Oral L-arginine also prevented development of hypertension and increased urinary excretion of cyclic GMP and nitrate in these rats. Dexamethasone, in a dose that prevented hypotension from parenteral injection of lipopolysaccharide, completely prevented the increase in excretion of cyclic GMP and nitrate, and hypertension resulted despite concomitant treatment with L-arginine. These studies supported an important role of dexamethasone-suppressible nitric oxide synthesis in the prevention of salt-sensitive hypertension in the Dahl/Rapp rat.
Chen
P Y
PY
Nephrology Research and Training Center, University of Alabama at Birmingham 35294-0007.
Sanders
P W
PW
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000097:blood / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002956:Citrulline / Q000097:blood; D006152:Cyclic GMP / Q000652:urine; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D006709:Homoarginine / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D007328:Insulin / Q000097:blood / Q000652:urine; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D009952:Ornithine / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D009566:Nitrates; D006709:Homoarginine; D002956:Citrulline; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D009952:Ornithine; D006152:Cyclic GMP