title: Alpha adrenergic activation and hemoglobin mediated contraction in the isolated rat thoracic aorta.
abstract: A primary mechanism for Hb mediated vascular contraction appears to be Hb scavenging of endothelium derive nitric oxide (NO), a potent vasodilator. In isolated rat thoracic aorta, however, Hb elicits contraction only after precontraction. The present study investigated a possible role of the alpha adrenergic activation in the Hb mediated contraction. Thoracic aortic rings harvested from normal male SD rats were prepared in a tissue bath and isometric tension changes were evaluated. In vessel rings precontracted with 50nM norepinephrine (NE), 1 microM Hb produced an additional 21.8+/-13.2% increase in tension. Pretreatment with 70nM phentolamine, an alpha adrenergic antagonist, prevented the 50nM NE induced contraction. In these vessels, subsequent treatment with 2-4 microM Hb did not elicit contraction. In vessel rings precontracted with 37mM KCl, 2 microM Hb produced an additional 21.8+/-20.1% tension increase (P<0.05). Pretreatment with phentolamine did neither prevent KCl induced contraction nor affect subsequent Hb mediated additional contraction. To test whether there is a threshold level of basal tension for Hb to trigger contraction, a group of vessel rings were passively stretched to match the tension generated by NE before Hb treatment. In these passively stretched vessel rings, Hb did not produce a significant contraction. Pretreatment with 10mM EGTA, a Ca++ chelator, significantly reduced NE induced contraction (9.7+/-5.9 vs 137.7+/-60.0%, P<0.01) but did not prevent it. EGTA also significantly reduced 2 microM Hb induced contraction (27.2+/-29.3% vs 8.9+/-7.7%, P<0.05). In contrast, pretreatment with verapamil, a Ca++ channel blocker, did not completely block NE and Hb induced contractions. In conclusion, alpha adrenergic activation is not a requisite for the Hb mediated contraction in isolated rat aortic rings. The mechanism how prior tone enhancement allows Hb mediated contraction remains unclear but results from this study suggest a factor that controls cytosolic Ca++ levels may be involved.
authors.affiliation: Brown University and The Miriam Hospital, Providence, RI 02906, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Tai
authors.forename: A G
authors.initials: AG
authors.lastname: Greenburg
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D001802:Blood Substitutes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D001802:Blood Substitutes; D002121:Calcium Channel Blockers; D006454:Hemoglobins; D012996:Solutions; D004533:Egtazic Acid; D014700:Verapamil; D002118:Calcium; D009638:Norepinephrine