(Hypertension. 1997;29:242.)
© 1997 American Heart Association, Inc.
Arthur C. Corcoran Memorial Lecture |
Asymmetrical Dimethylarginine, an Endogenous Nitric Oxide Synthase Inhibitor, in Experimental Hypertension
From the Departments of Internal Medicine III (H.M., K.K., O.T., Y.W., G.I., S.O., T.I.) and Pathology II (H.Y.), Kurume University School of Medicine, Fukuoka; the Hachi-ohji Laboratory, SRL (S.I.); and the Department of Nutrition, School of Medicine, University of Tokushima (M.K.), Japan.
Reprint requests to Hidehiro Matsuoka, MD, PhD, Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830, Japan
NG,NG-dimethyl-L-arginine (ADMA) is an endogenously synthesized nitric oxide (NO) synthase inhibitor which has potent pressor/vasoconstrictor effects. Dimethylargininase metabolizes ADMA to L-citrulline and plays a key role in determining the in vivo levels of ADMA. To investigate the role of ADMA in the pathogenesis of hypertension, we measured 24-hour urinary excretion of ADMA (UADMA) and nitrate/nitrite (NOx) in Dahl salt-sensitive hypertensive rats and spontaneously hypertensive rats (SHR). In Dahl salt-resistant rats, high-salt diet (8% NaCl) did not increase blood pressure and increased urinary NOx (P<.01) without changes in UADMA compared with low-salt diet (0.3% NaCl). In contrast, in Dahl salt-sensitive rats, high-salt diet increased blood pressure (P<.01), did not change urinary NOx excretion, and increased UADMA (P<.01). There was a significant (r=.65, P<.01) correlation between UADMA and the level of blood pressure in Dahl salt-sensitive rats. Plasma levels of NOx and ADMA and renal dimethylargininase content were comparable among them. These results may suggest that in Dahl salt-resistant rats, blood pressure is kept constant during high-salt intake, possibly due to the compensatory increased production of NO, and that in Dahl salt-sensitive rats, high-salt intake increases the production of ADMA, attenuates the compensatory increases in NO, and increases blood pressure. These results also suggest that the systemic production of ADMA is not dependent on renal dimethylargininase. SHR had significantly greater urinary NOx excretion (P<.05) and smaller UADMA than Wistar-Kyoto rats (P<.05), and UADMA was inversely correlated with their mean arterial pressure (r=.64, P<.05). In conclusion, ADMA, independently of the renal dimethylargininase content, may play a role in the pathogenesis in Dahl salt-sensitive hypertensive rats but not in SHR.
Key Words: blood pressure • Dahl • sodium • spontaneously hypertensive rats
Abbreviations: ADMA = NG,NG-dimethyl-L-arginine • DR = Dahl salt-resistant rats • DS = Dahl salt-sensitive rats • L-NMMA = NG-monomethyl-L-arginine • MAP = mean arterial pressure • NO = nitric oxide • NOx = nitrate/nitrite • SHR = spontaneously hypertensive rats • UADMA = 24-hour urinary excretion of ADMA • WKY = Wistar-Kyoto rats
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