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PLoS One ; 10(7): e0131424, 2015.
Article in English | MEDLINE | ID: mdl-26186712

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.


Subject(s)
Cationic Amino Acid Transporter 1/genetics , Dietary Fats/administration & dosage , Hypertension/metabolism , Obesity/metabolism , Stress, Psychological/metabolism , Sympathetic Nervous System/metabolism , Animals , Arterial Pressure/drug effects , Cationic Amino Acid Transporter 1/metabolism , Diet, High-Fat , Endothelium, Vascular/drug effects , Ganglionic Blockers/pharmacology , Gene Expression , Hypertension/etiology , Hypertension/genetics , Hypertension/physiopathology , Immobilization , Mice , Mice, Inbred C57BL , Mice, Transgenic , Obesity/etiology , Obesity/genetics , Obesity/physiopathology , Pentolinium Tartrate/pharmacology , Prunus dulcis/chemistry , Stress, Psychological/genetics , Stress, Psychological/physiopathology , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/physiopathology
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