title: Impaired hemorrhage tolerance in the obese Zucker rat model of metabolic syndrome.
abstract: As obese Zucker rats (OZR) manifesting the metabolic syndrome exhibit enhanced vascular adrenergic constriction and potentially an enhanced adrenergic activity vs. lean Zucker rats (LZR), this study tested the hypothesis that OZR exhibit an improved tolerance to progressive hemorrhage. Preliminary experiments indicated that, corrected for body mass, total blood volume was reduced in OZR vs. LZR. Anesthetized LZR and OZR had a cremaster muscle prepared for in situ videomicroscopy and had renal, splanchnic, hindlimb, and skeletal muscle perfusion monitored with flow probes. Arterial pressure, arteriolar reactivity to norepinephrine, and tissue/organ perfusion were monitored after either infusion of phentolamine or successive withdrawals of 10% total blood volume. Phentolamine infusion indicated that regional adrenergic tone under control conditions differs substantially between LZR and OZR, whereas with hemorrhage OZR exhibit decompensation in arterial pressure before LZR. Renal, distal hindlimb, and skeletal muscle perfusion decreased more rapidly and to a greater extent in OZR vs. LZR after hemorrhage. In contrast, hemorrhage-induced reductions in splanchnic perfusion in OZR lagged behind those in LZR, although a similar maximum reduction was ultimately attained. With increasing hemorrhage, cremasteric arteriolar tone increased more in OZR than LZR, and this increase in active tone was entirely due to an elevated adrenergic contribution. Norepinephrine-induced arteriolar constriction was greater in OZR vs. LZR under control conditions and during hemorrhage, with arterioles from OZR demonstrating early closure vs. LZR. These results suggest that a combination of reduced blood volume and elevated peripheral adrenergic constriction contribute to impaired hemorrhage tolerance in OZR.
authors.affiliation: Center for Interdisciplinary Research in Cardiovascular Science, Dept. of Physiology and Pharmacology, Robert C. Byrd Health Sciences Center, West Virginia Univ. School of Medicine, Morgantown, WV 26505, USA. jfrisbee@hsc.wvu.edu
authors.forename: Jefferson C
authors.initials: JC
authors.lastname: Frisbee
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000503:physiopathology*; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply; D009765:Obesity / Q000503:physiopathology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D010646:Phentolamine