Apocynin but not allopurinol prevented and reversed ACTH-induced hypertension in the rat. These results suggest superoxide production through NAD(P)H oxidase plays a role in ACTH-induced hypertension.

Chronic Dex treatment increased SBP and tended to increase oxidative stress shown as increased plasma F(2)-isoprostane concentrations. Tempol prevented and partially reversed Dex-induced hypertension, independent of improvement in systemic oxidative stress measured by F(2)-isoprostane concentrations.

In male SD rats, apocynin but not l-arginine prevented and reversed Dex-hypertension, suggesting that NAD(P)H oxidase-mediated superoxide production but not endothelial nitric oxide synthase uncoupling is important in Dex-hypertension.

The blood pressure-raising effects of adrenocortical steroids with predominantly glucocorticoid activity, both naturally occurring and synthetic, are well known. Recent evidence suggests that the nitric oxide system plays a key role in the hypertension produced by glucocorticoids. Glucocorticoid actions at various sites in the nitric oxide synthase (NOS) pathway may result in elevated blood pressure. These include: alterations in l-arginine availability or transport; NOS2 and NOS3 downregulation; reduced cofactor bioavailability; NOS uncoupling; a concomitant elevation in reactive oxygen species and removal of nitric oxide (NO) from the vascular environment; alterations in whole body antioxidant status; and erythropoietin induced resistance to NO.

1. Adrenocorticotrophic hormone (ACTH) raises blood pressure in humans, sheep, rat and mouse. In rat and humans, but not sheep, the hypertension can be explained by glucocorticoid excess. 2. In both rat and humans, the hypertension is associated with a rise in cardiac output and renal vascular resistance. 3. In both rat and humans, the nitric oxide system is implicated in glucocorticoid hypertension. 4. In both rat and humans, hypertension due to naturally occurring glucocorticoids is not prevented by drugs that block classical glucocorticoid or mineralocorticoid receptors. 5. Abnormalities in glucocorticoid metabolism may contribute to some forms of 'essential' hypertension.

ACTH-induced hypertension in the rat is associated with increased oxidative stress. Tempol treatment reversed, and pretreatment partially prevented ACTH-induced hypertension, independent of improvement in systemic oxidative stress.

1 We have identi®ed the P 2 receptors mediating vasomotor responses in the rabbit pulmonary artery. 2 Neither ATP nor UTP contracted intact or endothelium-denuded rings. However, both relaxed intact rings of rabbit pulmonary artery that had been preconstricted with phenylephrine (pD 2 5.2 and 5.6, respectively). 3 The vasodilator e ect of UTP was endothelium-dependent and abolished by the nitric oxide synthaseThe vasodilator e ect of ATP was only partially inhibited by removal of endothelium or addition of L-NOARG, suggesting an additional direct e ect on vascular smooth muscle. 5 The endothelium-dependent vasodilator responses to UTP and ATP were competitively antagonized by suramin. 6 Preconstricted, endothelium-denuded rings were also relaxed by 2-methylthio ATP (pD 2 6.6), a P 2Y receptor agonist. 7 Ca 2+ -mobilizing P 2U receptors were identi®ed on smooth muscle cells on the basis of single cell responses to ATP (pD 2 7.8) and UTP (pD 2 7.9; 6.7 in the presence of 100 mM suramin). 8 There was no evidence of a Ca 2+ -mobilizing P 2Y receptor in these cultured cells. 9 The data suggest the presence of (i) a suramin-sensitive P 2U receptor on endothelial cells that induces vasorelaxation through NO release, (ii) a suramin-sensitive P 2U receptor on cultured smooth muscle cells that mobilizes Ca 2+ but is not coupled to vasomotor responses and (iii) a putative P 2Y receptor on vascular smooth muscle cells that induces relaxation via a Ca 2+ -independent signal transduction pathway.

We investigated the effect of antioxidant N-acetylcysteine (NAC) on adrenocorticotropic hormone (ACTH)-hypertension. Male Sprague-Dawley rats received NAC (10 mg/L) or water 4 days before ACTH/saline treatment for 13 days (prevention study). In a reversal study, NAC commenced on day 8 of ACTH/saline treatment and continued for 5 days. ACTH increased systolic blood pressure (SBP) in water drinking rats (111 +/- 1 to 131 +/- 3 mmHg, p < 0.001). In the prevention study, NAC + ACTH increased SBP (108 +/- 2 to 120 +/- 2 mmHg, p < 0.001) but less than ACTH alone (p' < 0.05). In the reversal study, NAC had no significant effect (132 +/- 4 to 124 +/- 3 mmHg, ns). Thus, NAC partially prevented but did not reverse ACTH-induced hypertension.