title: Dahl SS rats demonstrate enhanced aortic perivascular adipose tissue-mediated buffering of vasoconstriction through activation of NOS in the endothelium.
abstract: Perivascular adipose tissue (PVAT) mediates buffering of vasoconstriction through activation of endothelium-derived factors. We hypothesized that the PVAT of Dahl salt-sensitive (Dahl SS) rats has reduced ability to buffer vasoconstriction. Vascular reactivity experiments were performed on aortic rings with PVAT intact (+PVAT) or removed (-PVAT), and endothelium intact (+ENDO) or removed (-ENDO) from Dahl SS rats and control SS.13(BN) rats (Dahl SS rats that have had chromosome 13 completely replaced with that of the Brown Norway rat, rendering this strain insensitive to high-salt or high-fat diet-induced hypertension). Endothelial dysfunction, assessed by ACh-mediated vasorelaxation, was confirmed in aortic rings of Dahl SS rats. The +PVAT+ENDO aortic rings had indistinguishable phenylephrine-induced vasoconstriction between genotypes. In both strains, removal of PVAT significantly enhanced vasoconstriction. Dahl SS rat -PVAT+ENDO aortic rings displayed exaggerated vasoconstriction to phenylephrine vs. SS.13(BN) rats, indicating that PVAT-mediated buffering of vasoconstriction was greater in Dahl SS rats. Removal of both the ENDO and PVAT restored vasoconstriction in both strains. The nitric oxide synthase (NOS) inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), produced a similar effect as that seen with -ENDO. These data indicate that the function of the PVAT to activate endothelium-derived NOS is enhanced in Dahl SS compared with SS.13(BN) rats and, most likely, occurs through a pathway that is distinct from ACh-mediated activation of NOS. PVAT weight and total PVAT leptin levels were greater in Dahl SS rats. Leptin induced a significantly decreased vasoconstriction in -PVAT+ENDO aortic rings from Dahl SS rats, but not SS.13(BN) rats. In contrast to our initial hypothesis, PVAT in Dahl SS rats buffers vasoconstriction by activating endothelial NOS via mechanisms that may include the involvement of leptin. Thus, the PVAT serves a vasoprotective role in Dahl SS rats on normal-salt diet.
authors.affiliation: Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
authors.forename: Frank T
authors.initials: FT
authors.lastname: Spradley
authors.affiliation: Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors.forename: Dao H
authors.initials: DH
authors.lastname: Ho
authors.affiliation: Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Medical College of Georgia, Georgia Regents University, Augusta, Georgia pollockj@uab.edu.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Pollock
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D050154:Adiposity; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020303:Rats, Inbred Dahl; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
keywords: aorta; endothelium; nitric oxide synthase; perivascular adipose tissue; phenylephrine; salt-senstive