title: The physiologic implications of isolated alpha(1) adrenergic stimulation.
abstract: Phenylephrine and methoxamine are direct-acting, predominantly α(1) adrenergic receptor (AR) agonists. To better understand their physiologic effects, we screened 463 articles on the basis of PubMed searches of "methoxamine" and "phenylephrine" (limited to human, randomized studies published in English), as well as citations found therein. Relevant articles, as well as those discovered in the peer-review process, were incorporated into this review. Both methoxamine and phenylephrine increase cardiac afterload via several mechanisms, including increased vascular resistance, decreased vascular compliance, and disadvantageous alterations in the pressure waveforms produced by the pulsatile heart. Although pure α(1) agonists increase arterial blood pressure, neither animal nor human studies have ever shown pure α(1)-agonism to produce a favorable change in myocardial energetics because of the resultant increase in myocardial workload. Furthermore, the cost of increased blood pressure after pure α(1)-agonism is almost invariably decreased cardiac output, likely due to increases in venous resistance. The venous system contains α(1) ARs, and though stimulation of α(1) ARs decreases capacitance and may transiently increase venous return, this gain may be offset by changes in afterload, venous compliance, and venous resistance. Data on the effects of α(1) stimulation in the central nervous system show conflicting changes, while experimental animal data suggest that renal blood flow is reduced by α(1)-agonists, and both animal and human data suggest that gastrointestinal perfusion may be reduced by α(1) tone.
authors.affiliation: Department of Anesthesiology, University of Virginia Health System, P.O. Box 800710, Charlottesville, VA 22908, USA. rht7w@virginia.edu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Thiele
authors.forename: Edward C
authors.initials: EC
authors.lastname: Nemergut
authors.forename: Carl
authors.initials: C
authors.lastname: Lynch
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000465:Algorithms; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001775:Blood Circulation / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003187:Compliance / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D006801:Humans; D008729:Methoxamine / Q000494:pharmacology; D008954:Models, Biological; D010656:Phenylephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D018924:Vascular Capacitance / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014680:Veins / Q000187:drug effects / Q000502:physiology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D010656:Phenylephrine; D008729:Methoxamine