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This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 297/3/H1140    most recent 00436.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhang, J. Articles by Blaustein, M. P. PubMed PubMed Citation Articles by Zhang, J. Articles by Blaustein, M. P.

Low-dose ouabain constricts small arteries from ouabain-hypertensive rats: implications for sustained elevation of vascular resistance

Departments of ¹Physiology and ²Medicine, and the ³Maryland Center for Heart, Hypertension and Kidney Disease, University of Maryland School of Medicine, Baltimore, Maryland

Submitted 11 May 2009 ; accepted in final form 13 July 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 (320 µm 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 ± 3 versus 124 ± 4 mmHg in controls (P < 0.01). Pressurized (70 mmHg) control and OH arteries, with only a single layer of myocytes, both had 165-µm internal diameters and 20-µm 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 µM) and high K⁺-induced vasoconstrictions and acetylcholine-induced vasodilation were comparable in control and OH arteries. Vasoconstrictions induced by 5 µM phenylephrine and by 10 mM caffeine in Ca²⁺-free media indicated that releasable sarcoplasmic reticulum Ca²⁺ stores were normal in OH arteries. Importantly, 100 nM ouabain constricted both control and OH arteries by 26 µm, indicating that this response was not downregulated in OH rats. This maximal ouabain-induced constriction corresponds to a 90% increase in resistance to flow in these small arteries; thus ouabain at EC₅₀ of 0.66 nM should raise resistance by 35%. 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