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

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 297; no. 3; pp. H1140 - H1150
• Main Authors: Zhang, Jin, Hamlyn, John M, Karashima, Eiji, Raina, Hema, Mauban, Joseph R. H, Izuka, Michelle, Berra-Romani, Roberto, Zulian, Alessandra, Wier, W. Gil, Blaustein, Mordecai P
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2009
• Subjects: Acetylcholine - pharmacology; Animals; Blood Pressure - drug effects; Blood Pressure - physiology; Caffeine - pharmacology; Calcium - metabolism; Coronary vessels; Dose-Response Relationship, Drug; Drug therapy; Enzyme Inhibitors - pharmacology; Hypertension; Hypertension - chemically induced; Hypertension - physiopathology; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; Ouabain - pharmacology; Phenylephrine - pharmacology; Phosphodiesterase Inhibitors - pharmacology; Potassium - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Sarcoplasmic Reticulum - metabolism; Vascular Resistance - drug effects; Vascular Resistance - physiology; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00436.2009

Departments of 1 Physiology and 2 Medicine, and the 3 Maryland 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 Ca 2+ -free media indicated that releasable sarcoplasmic reticulum Ca 2+ 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 EC 50 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 Address for reprint requests and other correspondence: J. Zhang, Dept. of Physiology, Univ. of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201 (e-mail: jzhan002{at}umaryland.edu )