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(Hypertension. 2002;39:662.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Nitric Oxide Produced by THAL Nitric Oxide Synthase Inhibits TGF

Hong Wang; Oscar A. Carretero; Jeffrey L. Garvin

From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich.

Correspondence to Dr Jeffrey L. Garvin, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202. E-mail: jgarvin1{at}hfhs.org

Nitric oxide (NO) produced by neuronal NO synthase (nNOS) in the macula densa decreases tubuloglomerular feedback (TGF). NO produced by NOS in the thick ascending limb (THAL) inhibits NaCl transport. We hypothesized that NO produced by NOS in the THAL reaches the macula densa and inhibits TGF. Rabbit afferent arterioles and attached macula densa were simultaneously microperfused in vitro. TGF response was determined by measuring afferent arteriole diameter before and after increasing NaCl in the macula densa perfusate. When the nNOS inhibitor 7-nitroindazole (7-NI) (10 µmol/L) was added to the macula densa lumen, it increased TGF from 2.3±0.2 to 3.5±0.5 µm (P<0.02; n=6). In the presence of 7-NI, N-nitro-L-arginine methyl ester (L-NAME) (1 mmol/L) enhanced TGF from 2.6±0.3 to 4.0±0.5 µm (P<0.02; n=6) when the macula densa was perfused orthograde via the THAL, whereas it had no effect on TGF when the macula densa was perfused retrograde via the distal tubule (DT). Inhibition of macula densa soluble guanylate cyclase with LY83583 (1 µmol/L) blocked the effect of NO produced by THAL NOS when the macula densa was perfused via the THAL. We concluded that NO produced by THAL NOS acts as a paracrine factor, reaching the macula densa and inhibiting TGF.

Key Words: nitric oxide • rabbits • arterioles

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