Active myogenic tone: a requisite for hemoglobin mediated vascular contraction?
Acellular free hemoglobin (Hb), when intravenously administered to animals and humans, elicits vascular contraction. A primary mechanism for the Hb mediated vasoconstriction is Hb scavenging of nitric oxide (NO), a potent relaxation factor, constitutively secreted by the vascular endothelium. However, in the isolated rat thoracic aorta in basal state, Hb does not elicit contraction. To investigate this apparent paradox, we assessed isolated rat aortic ring isometric contraction responses to Hb under different myogenic tone states: (1) following equilibration at a submaximal tension, (2) following agonist induced contraction, or (3) following a passive mechanical stretch. In vessel rings at basal state, Hb as high as 4 microM did not elicit any measurable contractions. In contrast, in vessel rings tone enhanced with norepinephrine, Hb as low as 0.1 microM Hb elicited a significant additional contraction. In vessel rings with passively induced tone, 4 microM Hb did not elicit a notable contraction. Similarly, in vessel rings in basal state, 0.17-1 mM acetylcholine, a NO dependent vasodilator, did not elicit relaxation. In these vessel rings, exogenous 8-Br-cGMP, a membrane permeable cGMP analog, did not elicit relaxation. In conclusion, in the isolated rat thoracic aorta, Hb mediated contraction may be contingent upon the state of myogenic tone.
Kim
H W
HW
Brown University School of Medicine and The Miriam Hospital Providence, RI 02906, USA. hae_kim@brown.edu
Tai
J
J
Greenburg
A G
AG
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D001802:Blood Substitutes / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D001802:Blood Substitutes; D006454:Hemoglobins; D014662:Vasoconstrictor Agents; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006152:Cyclic GMP; D009638:Norepinephrine