Hypertension (HT) with chronic nitric oxide blockade (NOB).

Chronic administration of L-arginine analogs such as L-NAME, produce a dose dependent hypertension due to chronic NOB. Malignant hypertension develops with high levels of NOB. NO deficiency is not the only component of this HT since the SNS and renin/All are also involved in maintenance of the high BP. Chronic NOB also causes renal damage and dysfunction including renal vasoconstriction, arteriolar and glomerular damage leading to falls in GFR and proteinuria, all of which exacerbate the HT. It has been suggested that chronic NOB produces a volume dependent model of HT, however, we find that chronic NOB with high dose L-NAME results in volume depletion and that the HT is due to vasoconstriction. NO blockers such as L-NAME inhibit NO synthesis from endothelial, neuronal and inducible NO synthases. Inhibition of NO from all these sources may contribute to the genesis of the hypertension due to NOB by separate mechanisms. Until more selective, NO synthase isoform selective blockers are available, the relative cardiovascular and renal importance of NO from the various NO synthases, remains unknown