Collectively, these data indicate that obesity-induced down-regulation of CAT1 expression and subsequent reduced bioavailability of nitric oxide may contribute to the development of obesity-induced hypertension.

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.

No abstract

Cationic amino acid transporter‐1 (CAT‐1) is the predominant L‐arginine transporter expressed in endothelial cells. We hypothesised endothelial CAT‐1 over‐expression can ameliorate obesity induced hypertension. With the use of telemetry, baseline mean arterial pressure (MAP) and responses of MAP to the ganglionic blocker, pentolinium (5 mg/kg) were measured in conscious wild type mice (WT; n = 10) and mice over expressing endothelial CAT1 (CAT+; n=15) fed a normal or a high fat diet for 20 weeks. Both genotypes of mice developed obesity when placed on a high fat diet (Pdiet ≤ 0.007). MAP was greater by 12 ± 2 mmHg (Pdiet < 0.001) in WT mice fed a high fat diet, compared to those fed a normal fat diet. In contrast, MAP was not significantly different in CAT+ mice fed a normal or a high fat diet (Pdiet*genotype= 0.002). Reduction in MAP to pentolinium was greater in WT mice fed a high fat diet (−27 ± 2 mmHg), compared to WT mice fed a normal fat diet (−16 ± 2 mmHg; Pdiet = 0.004) suggesting that the obesity induced hypertension is due to increased activity of the sympathetic nervous system. In CAT+ mice, MAP responses to pentolinium were similar in mice fed a normal or a high fat diet (Pdiet = 0.7; Pdiet*genotype=0.01). These data suggest that endothelial CAT1 over expression can separate obesity from hypertension by buffering the activity of the sympathetic nervous system.

Cationic amino acid transporter‐1 (CAT‐1) is the predominant L‐arginine transporter expressed in endothelial cells. We hypothesised endothelial CAT‐1 over‐expression can ameliorate obesity induced hypertension.With the use of telemetry, baseline mean arterial pressure (MAP) and responses of MAP to the ganglionic blocker, pentolinium (5 mg/kg) were measured in conscious wild type mice (WT; n = 10) and mice over expressing endothelial CAT1 (CAT+; n=15) fed a normal or a high fat diet for 20 weeks.Both genotypes of mice developed obesity when placed on a high fat diet (Pdiet ≤ 0.007). MAP was greater by 12 ± 2 mmHg (Pdiet < 0.001) in WT mice fed a high fat diet, compared to those fed a normal fat diet. In contrast, MAP was not significantly different in CAT+ mice fed a normal or a high fat diet (Pdiet*genotype= 0.002). Reduction in MAP to pentolinium was greater in WT mice fed a high fat diet (−27 ± 2 mmHg), compared to WT mice fed a normal fat diet (−16 ± 2 mmHg; Pdiet = 0.004) suggesting that the obesity induced hypertension is due to increased activity of the sympathetic nervous system. In CAT+ mice, MAP responses to pentolinium were similar in mice fed a normal or a high fat diet (Pdiet = 0.7; Pdiet*genotype=0.01). These data suggest that endothelial CAT1 over expression can separate obesity from hypertension by buffering the activity of the sympathetic nervous system.