title: Temporal alterations in peripheral vascular responsiveness during both the development and recovery from pacing-induced heart failure.
abstract: The responsiveness of both the in vitro dorsal pedal artery and in vitro saphenous vein to alpha-adrenergic agents and prostaglandin F2 alpha was evaluated at baseline (prior to the onset of rapid ventricular pacing), at 1 week of pacing (mild heart failure), and 4 weeks after pacing when there was recovery from congestive heart failure. Eleven dogs were paced at 250 beats/min for 1 week and 7 dogs were paced for 3 weeks at 250 beats/min and allowed to recover from pacing for a further 4 weeks. At 1 and 4 weeks of recovery, compared to control, the maximal responsiveness of the dorsal pedal artery to norepinephrine was increased from 5.7 +/- 0.9 to 12.9 +/- 3.3 and 18.6 +/- 1.0 g/mm2, respectively. A similar finding was observed in the saphenous vein. The response of the artery to the selective alpha 1-agonist, phenylephrine, was also enhanced at 1 week. Moreover, the response of the artery and vein to phenylephrine was enhanced further at 4 weeks of recovery. In contrast, the response to the selective alpha 2-agonist, BHT 920, remained unaltered at these time points compared to control. Oxymetazoline, an agent used to differentiate between alpha 1-subdivisions, produced a significantly higher maximal response at 4 weeks of recovery (18.4 +/- 1.6 g/mm2 for the artery and 27.7 +/- 2.6 g/mm2 for the vein) compared to control (8.2 +/- 0.5 g/mm2 for the artery and 10.3 +/- 0.8 g/mm2 for the vein). The artery also displayed lower EC50 values for norepinephrine and phenylephrine at 1 week (0.7 and 2.2 microM, respectively) and 4 weeks of recovery (0.9 and 3.1 microM, respectively) compared to control (6.0 and 9.0 microM, respectively). In contrast, the only significant decreases in EC50's in the vein were the norepinephrine and oxymetazoline at 1 week of pacing (0.2 and 0.06 microM, respectively) compared to control (1.5 and 0.09 microM, respectively). The maximal tension developed to PGF2 alpha was enhanced after 1 week of pacing in both vessels and persisted 4 weeks following the cessation of pacing. Compared with control, EC50 values for PGF2 alpha were decreased at 1 and 4 weeks of recovery. We conclude that differences exist in peripheral vascular reactivity to both alpha 1-adrenoceptor agents and PGF2 alpha at 1 week of pacing and 4 weeks of recovery from pacing. Furthermore, the subtle reactivity differences between the artery and vein reflect different populations of alpha 1-adrenoceptors possibly associated with different signal transduction processes.
authors.affiliation: Division of Cardiology, St Michael's Hospital, University of Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Forster
authors.forename: P M
authors.initials: PM
authors.lastname: Campbell
authors.forename: P W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology; D001381:Azepines / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D015237:Dinoprost / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005528:Foot / Q000098:blood supply; D006333:Heart Failure / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000316:Adrenergic alpha-Agonists; D001381:Azepines; C024763:talipexole; D010109:Oxymetazoline; D015237:Dinoprost; D009638:Norepinephrine