title: Low-affinity hemoglobin increases tissue PO2 and decreases arteriolar diameter and flow in the rat cremaster muscle.
abstract: The hypothesis that tissue oxygen delivery in excess of metabolic demand results in vasoconstriction and reduced blood flow was tested in the cremaster muscle of anesthetized Sprague-Dawley rats by studying the effects of an intravenous infusion of RSR-13, an allosteric effector of hemoglobin. RSR-13 reduces the affinity of hemoglobin for oxygen, causing a right shift in the oxygen dissociation curve. Thus, oxygen delivery to the tissues was increased without elevations in blood flow or blood pressure. Tissue PO2, arteriolar diameter, and RBC velocity were measured and volume flow was calculated from diameter and RBC velocity in third-order arterioles. In rats receiving RSR-13 at a rate of 200 mg kg-1 in 15 min (n = 18) P50 (the PO2 at which hemoglobin is 50% saturated) increased from 36 +/- 1 to 52 +/- 3 mm Hg, and tissue PO2 increased to a maximum of 146 +/- 12% above its control value. P50 and tissue PO2 did not change in the control group (n = 8) receiving vehicle at a rate equivalent to that in the experimental group. In a separate group of rats receiving RSR-13 (n = 7), P50 increased from 38 +/- 1 to 51 +/- 3 mm Hg, calculated arteriolar flow decreased from 9 +/- 3 to a minimum of 1.4 +/- 1 nl sec-1, and arteriolar diameter decreased from 27 +/- 3 to a minimum of 13 +/- 3 micrograms P50, volume flow, and arteriolar diameter did not change in the control group (n = 10). These results suggest that an increased tissue oxygen delivery, caused by a right shift in the oxygen dissociation curve, may cause an increase in vascular resistance independent of an elevated blood flow.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Kunert
authors.forename: J F
authors.initials: JF
authors.lastname: Liard
authors.forename: D J
authors.initials: DJ
authors.lastname: Abraham
authors.forename: J H
authors.initials: JH
authors.lastname: Lombard
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D001783:Blood Flow Velocity; D006454:Hemoglobins / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D010100:Oxygen / Q000097:blood / Q000493:pharmacokinetics*; D010313:Partial Pressure; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000814:Aniline Compounds; D006454:Hemoglobins; D011422:Propionates; C067396:efaproxiral; D010100:Oxygen