Angiotensin-converting enzyme inhibitors and AT(1)-receptor antagonist restore nitric oxide synthase (NOS) activity and neuronal NOS expression in the adrenal glands of spontaneously hypertensive rats

During development of hypertension in spontaneously hypertensive (SHR) rats , the activity of adrenal nitric oxide synthase (NOS) was investigated. SHR and Wistar-Kyoto (WKY) rats were studied at different ages: 3 - 4, 7 - 8 a nd 12 - 13 weeks after birth. Basal NOS activity was measured by the abilit y of homogenate to convert [H-3]-L-arginine to [H-3]-L-citrulline. At all a ges, SHR rats exhibited 50 - 60% reduction in NOS activity when compared to age-matched WKY rats. In a following study, SHR rats (12-13 weeks) were tr eated chronically with the angiotensin I-converting enzyme inhibitors (ACE- I) captopril or enalapril, or the AT(1)-receptor antagonist losartan (2 x 2 5, 10 and 60 mg/kg per day for 10 days, respectively). The total NOS activi ty and protein expression of NOS isoenzymes from adrenals were determined. The basal NOS activity and protein expression of neuronal NOS (nNOS) was si gnificantly increased in treated SHR rats when compared to control rats. Th e isoforms endothelial NOS and inducible NOS were undetectable. We conclude that impaired NO synthesis in the adrenal glands of SHR rats may contribut e to the onset and maintenance of hypertension. The upregulation of nNOS pr otein in the adrenal glands may be one of the mechanisms by which ACE inhib itors and AT1-receptor antagonists by restoring the NO synthesis, mediate t heir antihypertensive effects.