Effects of chronic neuronal nitric oxide-synthase inhibition on arterial function and structure in spontaneously hypertensive rats.

While the effect of chronic non-specific NO-synthase inhibition in the cardiovascular system has been recognized under normotensive and hypertensive conditions, there are no data relating the long-term inhibition of neuronal NO-synthase (nNOS) in essential hypertension. The aim of this study was to investigate the long-term effect of nNOS inhibitor 7-nitroindazole (7-NI) administration on arterial function and structure in spontaneously hypertensive rats (SHR). Ten weeks old SHR were divided in two groups: control group and group administered 7-NI (10 mg/kg/day) for six weeks in drinking water. Systolic blood pressure (SBP) was measured using the plethysmographic method. The vasoactivity of isolated thoracic aorta (TA) and mesenteric artery (MA) was recorded via changes in isometric tension, and the geometry of both arteries was measured using light microscopy. Chronic treatment with 7-NI did not affect either SBP or heart/body weight ratio. Acetylcholine-induced relaxation of both arteries was unchanged after 7-NI. 7-NI administration did not affect the sensitivity and contraction to exogenous noradrenaline in TA, whereas both parameters were augmented in MA. The contractile response of MA induced by transmural nerve stimulation (endogenous noradrenaline) was unaffected after 7-NI. The mass of TA wall was unchanged, whereas hypertrophy was observed in MA after 7-NI. In summary, although SBP and endothelial function were not changed after chronic nNOS inhibition, the contractile and structural properties of TA and MA were affected differently. The data suggest that nNOS triggers original and tissue-specific regulatory pathways in essential hypertension.