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CARDIOVASCULAR

Phenylpropanolamine Constricts Mouse and Human Blood Vessels by Preferentially Activating 2-Adrenoceptors

Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio

Phenylpropanolamine (dl-norephedrine) was one of the most widely used therapeutic agents to act on the sympathetic nervous system. Because of concerns regarding incidents of stroke, its use as a nasal decongestant was discontinued. Although considered an ₁-adrenergic agonist, the vascular adrenergic pharmacology of phenylpropanolamine was not fully characterized. Unlike most other circulations, the vasculature of the nasal mucosa is highly enriched with constrictor ₂-adrenoceptors. Therefore, experiments were performed to determine whether phenylpropanolamine activates vascular ₂-adrenoceptors. Mouse tail and mesenteric small arteries and human small dermal veins were isolated and analyzed in a perfusion myograph. The selective ₁-adrenergic agonist phenylephrine caused constriction of tail and mesenteric arteries and human veins. The selective ₂-adrenergic agonist UK14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine] caused constriction in tail arteries and in human veins, but not mesenteric arteries. The lack of constriction to UK14,304 was also observed in endothelium-denuded mesenteric arteries. Phenylpropanolamine constricted both types of artery but was 62-fold more potent in tail arteries. In mesenteric arteries, constriction to phenylpropanolamine was not affected by the selective ₂-adrenergic antagonist, rauwolscine (10^-7 M) but was abolished by the selective ₁-adrenergic antagonist, prazosin (3 x 10^-7 M). In contrast, constriction to phenylpropanolamine in tail arteries and in human veins was inhibited by rauwolscine but not prazosin. Therefore, phenylpropanolamine is a preferential ₂-adrenergic agonist. At low concentrations, it constricts blood vessels that express functional ₂-adrenoceptors, whereas at much higher concentrations, phenylpropanolamine also activates vascular ₁-adrenoceptors. This action likely contributed to phenylpropanolamine's therapeutic activity, namely constriction of the nasal vasculature.

Address correspondence to: Dr. Nicholas A. Flavahan, Heart and Lung Research Institute, 473 West 12th Avenue, Room 110E, Columbus OH 43210. E-mail: flavahan-1{at}medctr.osu.edu

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