Low-dose ouabain constricts small arteries from ouabain-hypertensive rats: implications for sustained elevation of vascular resistance. Am J Physiol Heart Circ Physiol 297: H1140 -H1150, 2009. First published July 17, 2009 doi:10.1152/ajpheart.00436.2009.-Prolonged ouabain administration to normal rats causes sustained blood pressure (BP) elevation. This ouabain-induced hypertension (OH) has been attributed, in part, to the narrowing of third-order resistance arteries (ϳ320 m internal diameter) as a result of collagen deposition in the artery media (see Ref. 6). Here we describe the structural and functional properties of fourth-order mesenteric small arteries from control and OH rats, including the effect of low-dose ouabain on myogenic tone in these arteries. Systolic BP in OH rats was 138 Ϯ 3 versus 124 Ϯ 4 mmHg in controls (P Ͻ 0.01). Pressurized (70 mmHg) control and OH arteries, with only a single layer of myocytes, both had ϳ165-m internal diameters and ϳ20-m wall thicknesses. Even after fixation, despite vasoconstriction, the diameters and wall thicknesses did not differ between control and OH fourth-order arteries, whereas in third-order arteries, both parameters were significantly smaller in OH than in controls. Myogenic reactivity was significantly augmented in OH fourth-order arteries. Nevertheless, phenylephrine-(1 M) and high K ϩ -induced vasoconstrictions and acetylcholine-induced vasodilation were comparable in control and OH arteries. Vasoconstrictions induced by 5 M phenylephrine and by 10 mM caffeine in Ca 2ϩ -free media indicated that releasable sarcoplasmic reticulum Ca 2ϩ stores were normal in OH arteries. Importantly, 100 nM ouabain constricted both control and OH arteries by ϳ26 m, indicating that this response was not downregulated in OH rats. This maximal ouabain-induced constriction corresponds to a ϳ90% increase in resistance to flow in these small arteries; thus ouabain at EC 50 of ϳ0.66 nM should raise resistance by ϳ35%. We conclude that dynamic constriction in response to circulating nanomolar ouabain in small arteries likely makes a major contribution to the increased vascular tone and BP in OH rats. myogenic reactivity; resistance artery OUABAIN, A MAMMALIAN adrenocortical hormone (4,20,21,28), apparently plays an important role in the pathogenesis of hypertension in humans and rodents. About 50% of patients with essential hypertension and a majority of patients with adrenocortical adenomas and hypertension have elevated plasma endogenous ouabain (EO) (42,45). In normal humans, ouabain infusion increases peripheral vascular resistance, reduces blood flow, and elevates blood pressure (BP) (35, 47).Moreover, high-dietary salt increases plasma EO levels in normal men (32).Elevated EO levels are also observed in rats with DOCA-salt hypertension (20), reduced renal mass hypertension (24), and Milan strain hypertension (14). Additionally, the chronic treatment of normal rats and mice with ouabain elevates BP, i.e., ouabain-induced hypertension (OH) (12, 33, 50). Although digoxin, lik...