title: Vascular smooth muscle responsiveness to noradrenaline and phenylephrine following experimental heart failure in dogs.
abstract: Adrenergic vascular responsiveness was assessed in the dorsal pedal artery and the saphenous vein in dogs before and after the development of congestive heart failure (CHF). Following development of severe CHF, both noradrenaline and phenylephrine could produce a greater maximum tension and a shift of the resultant concentration-effect curve to the left compared to the curves seen before the development of CHF. The saphenous vein was more sensitive than the dorsal pedal artery to both agonists before CHF. After CHF, the sensitivity difference to noradrenaline increased significantly but it remained unaltered to phenylephrine. Relative to noradrenaline, phenylephrine became more potent on the artery at peak CHF, whereas the potency ratio was unchanged in the saphenous vein at peak CHF. Prazosin was a competitive antagonist only against phenylephrine prior to CHF; competitive antagonism was not seen against noradrenaline or following CHF. Prazosin was less effective in antagonising noradrenaline induced contractions, as shown by an increase in IC50 values. These results are consistent with increased tissue sensitivity to adrenergic agents during CHF. The greater potency of phenylephrine in the artery at peak CHF suggests the presence of a greater proportion of alpha 1 adrenoceptors, which is consistent with the decrease in effectiveness of prazosin after the development of CHF.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Forster
authors.forename: S
authors.initials: S
authors.lastname: Carter
authors.forename: P
authors.initials: P
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D004285:Dogs; D005528:Foot / Q000098:blood supply; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects / Q000503:physiopathology
chemical_list: D010656:Phenylephrine; D009638:Norepinephrine