Hemoglobin mediated contraction of the isolated rat thoracic aorta: why is precontraction necessary?
A primary mechanism for the hemoglobin (Hb) mediated vascular contraction is believed to be Hb scavenging of endothelial nitric oxide (NO). In the isolated rat thoracic aorta, however, the Hb mediated contraction occurs only after an agonist-induced precontraction. Why? To investigate the question, a rat thoracic aortic ring model was used. Isometric vessel ring tension responses to selected pharmacologic contractile agonists were assessed and compared. The Hb mediated additional contraction occurred in vessel rings precontracted with adrenergic agonists as well as other types of contractile agonists. Even after agonist induced contraction, removal of the vascular endothelium or inhibition of endothelial NO synthase with Nomega-nitro-L-arginine methyl ester prevented the Hb mediated additional contraction. Additionally, imposition of passive tension without an agonist pretreatment did not allow Hb mediated contraction. In conclusion, in the isolated rat thoracic aorta, the endothelial NO synthase is minimally active in the basal state but upregulated upon treatment with a contractile agonist. This may explain why the Hb mediated additional contraction occurs only after an agonist induced precontraction.
Kim
H W
HW
Brown University and The Miriam Hospital, Providence, RI 02906, USA. Hae_Kim@Brown.edu
Greenburg
A G
AG
D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006454:Hemoglobins; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009924:Organ Culture Techniques; D010108:Oxyhemoglobins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000322:Adrenergic Agonists; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D008706:Methemoglobin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester