title: Different effects of in vivo ouabain and digoxin on renal artery function and blood pressure in the rat.
abstract: To investigate vascular mechanisms in hypertension, we isolated renal arterial rings from rats with ouabain-dependent hypertension and studied their function. In rats infused with ouabain for 5 weeks, systolic and mean blood pressures (BP) were increased relative to controls. Contractions evoked by high KCl solutions were greater in rings from ouabain-infused rats whereas the threshold concentrations and EC50s for KCl and the peak caffeine contractures were not different. KCl contractures were not affected by 5 microM prazosin. Phenylephrine contractures were increased marginally in ouabain-infused rats, while acetylcholine-induced relaxation was normal. In vitro superfusion of rings with 10 nM ouabain or digoxin did not affect the measured parameters. Plasma ouabain, BP, and all evoked responses were normal one week following interruption of the ouabain infusion. In a second study, BP increased in ouabain (15 microg/kg/day, n= 23), but not digoxin (30 microg/kg/day, n=12), or vehicle-infused (n=16) rats. KCl contractures were greater in rings from ouabain-but decreased in rings from digoxin-infused rats, respectively and correlated with systolic and mean BP (r=0.69, n=30, p<0.005). Peak caffeine (25 mM) responses were similar but the area under the contraction was reduced in the vessels from ouabain-infused rats and correlated inversely with MBP (r=-0.47, n=33, p<0.02). We conclude that a voltage-dependent component of tone in the rat renal artery is reversibly and specifically augmented by in vivo administration of ouabain whereas it is diminished by in vivo digoxin. Vascular production of and response to nitric oxide does not appear to be impaired in the ouabain model. Alterations of intracellular Ca2+ storage and Ca2+ influx in response to in vivo ouabain may underlie the increase in renal vascular resistance and hypertension in this model. The opposite effects of ouabain and digoxin on the hemodynamic and vascular parameters in this study indicate that these agents have novel mechanisms of action in vivo that may not be mediated exclusively by sodium-potassium pumps.
authors.affiliation: Department of Physiology, School of Medicine, University of Maryland, Baltimore 21201, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: P
authors.initials: P
authors.lastname: Manunta
authors.forename: B P
authors.initials: BP
authors.lastname: Hamilton
authors.forename: J M
authors.initials: JM
authors.lastname: Hamlyn
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D002298:Cardenolides; D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology*; D004077:Digoxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D010042:Ouabain / Q000097:blood / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012503:Saponins / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002298:Cardenolides; D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D012503:Saponins; D014665:Vasodilator Agents; C034504:digoxin-like factors; D010656:Phenylephrine; D002110:Caffeine; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D011188:Potassium