Increased Constrictor Tone Induced by Ouabain-Treatment in Rats.
ABSTRACT Ouabain-induced hypertension in rodents provides a model to study cardiovascular changes associated with human hypertension. We examined vascular function in rats after long-term treatment with ouabain. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in male Sprague-Dawley rats treated with ouabain (Oua, ∼25 µg·day) or placebo for 8 weeks. Blood pressure increased in ouabain-treated animals, reaching 30% above baseline SBP after 7 weeks. At the end of treatment, vascular responses were studied in mesenteric resistance arteries (MRA) by wire myography. Contraction to potassium chloride (KCl) in intact and denuded arteries showed greater sensitivity in Oua-treated animals. Contraction to phenylephrine (PE) and relaxation to acetylcholine (ACh) were similar between groups with a lower response to sodium nitroprusside (SNP) in Oua-treated arteries. Sensitivity to endothelin-1 (ET-1) was higher in Oua-treated arteries. Na-K ATPase activity was decreased in MRA from Oua-treated animals, whereas protein expression of the Na-K-ATPase α2 isoform was increased in heart and unchanged in mesenteric artery. Pre-incubation with indomethacin (10M) or L-NAME (10M) abolished the differences in KCl response and Na-K ATPase activity. Changes in MRA are consistent with enhanced vascular smooth muscle cell reactivity, a contributor to the increased vascular tone observed in this model of hypertension.
Full-textDOI: · Available from: Victor M Pulgar, Jan 22, 2015
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ABSTRACT: Ouabain is a cardiac glycoside produced in the adrenal glands and hypothalamus. It affects the function of all cells by binding to Na+/K+-ATPase. Several lines of evidence suggest that endogenous ouabain could be involved in the pathogenesis of essential (particularly, salt-sensitive) hypertension. However, information regarding the postulated hypertensive effect of the long-term administration of low-dose exogenous ouabain is inconsistent. This study was designed to help settle this controversy through the use of telemetric monitoring of arterial blood pressure and to elucidate the ouabain-induced alterations that could either promote or prevent hypertension. Ouabain (63 and 324 µg/kg/day) was administered subcutaneously to male Wistar rats. Radiotelemetry was used to monitor blood pressure, heart rate and measures of cardiovascular variability and baroreflex sensitivity. The continuous administration of ouabain for 3 months did not elevate arterial blood pressure. The low-frequency power of systolic pressure variability, urinary excretion of catecholamines, and cardiovascular response to restraint stress and a high-salt diet as well as the responsiveness to α1-adrenergic stimulation were all unaltered by ouabain administration, suggesting that the activity of the sympathetic nervous system was not increased. However, surrogate indices of cardiac vagal nerve activity based on heart rate variability were elevated. Molecular remodeling in mesenteric arteries that could support the development of hypertension (increased expression of the genes for the Na+/Ca2+ exchanger and Na+/K+-ATPase α2 isoform) was not evident. Instead, the plasma level of vasodilatory calcitonin gene-related peptide (CGRP) significantly rose from 55 (11, SD) in the control group to 89 (20, SD) pg/ml in the ouabain-treated rats (PTukey's = 18.10-5). These data show that long-term administration of exogenous ouabain does not necessarily cause hypertension in rodents. The augmented parasympathetic activity and elevated plasma level of CGRP could be linked to the missing hypertensive effect of ouabain administration.PLoS ONE 10/2014; 9(10):e108909. DOI:10.1371/journal.pone.0108909 · 3.53 Impact Factor