Salt-induced hypertension in Dahl salt-resistant and salt-sensitive rats with NOSII inhibition

Although recent evidence suggests that reduced nitric oxide (NO) production maybe involved in salt-induced hypertension, the specific NO synthase (NOS ) responsible for the conveyance of salt sensitivity remains unknown. To de termine the role of inducible NOS (NOS II) in salt-induced hypertension, we treated Dahl salt-resistant (DR) rats with the selective NOS II inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) for 12 days. Tail-cuff s ystolic blood pressures rose 29 +/- 6 and 42 +/- 8 mmHg in DR rats given 15 0 and 300 nmol AMT/h, respectively (P < 0.01, 2-way ANOVA) after 7 days of 8% NaCl diet. We observed similar results with two other potent selective N OS II inhibitors, S-ethylisourea (EIT) and N-[3-(aminomethyl)benzyl]acetami dine hydrochloride (1400W). Additionally, AMT effects were independent of a lterations in endothelial function as assessed by diameter change of mesent eric arterioles in response to methacholine using videomicroscopy. We, ther efore, conclude from those data that NOS II is important in salt-induced hy pertension.