title: Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice.
abstract: Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1) can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS) on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13) and CAT1 overexpressing mice (CAT+; n=13) were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP) and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p.) on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%). The depressor response to pentolinium was 65% greater in obese WT than lean WT (P < 0.001), but was similar in obese and lean CAT+ (P = 0.65). In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ≤ 0.001). Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ≤ 0.001), but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%), but greater in obese CAT+ (37 ± 2%), when compared to respective lean WT (31 ± 3%) and lean CAT+ controls (27 ± 2%; P ≤ 0.02). We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Niwanthi W
authors.initials: NW
authors.lastname: Rajapakse
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Florian
authors.initials: F
authors.lastname: Karim
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Evans
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects; D005730:Ganglionic Blockers / Q000494:pharmacology; D015870:Gene Expression; D006973:Hypertension / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007103:Immobilization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010425:Pentolinium Tartrate / Q000494:pharmacology; D000068181:Prunus dulcis / Q000737:chemistry; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D027201:Cationic Amino Acid Transporter 1; D004041:Dietary Fats; D005730:Ganglionic Blockers; C420826:Slc7a1 protein, mouse; D010425:Pentolinium Tartrate