Abstract P227: A High Fat Diet Does Not Enhance Blood Pressure Dependence On Chemerin In Normotensive Rats

Abstract

Various humoral factors produced by adipose tissue are suggested to contribute to obesity associated hypertension and cardiovascular pathology. The adipokine chemerin is a frontrunner candidate. Male Dahl SS rats fed a high fat (HF; 60% kCal) diet from weaning develop severe hypertension that is profoundly reduced by weekly treatment with an antisense oligonucleotide (ASO) that disables chemerin mRNA. Here we hypothesized that feeding a HF diet from weaning to male Sprague Dawley (SD) rats would similarly increase the dependence of blood pressure (BP) regulation on chemerin. Over 17 weeks of feeding, HF fed SD rats gained significantly more weight and body fat than those fed control (10% kCal) diet. Radiotelemeters were implanted at 17 weeks of age to measure BP. Two weeks of basal BP was collected, and as we and others have shown previously, the HF diet did not increase BP in SD rats (control = 117±2.5 mm Hg; HF = 122±2.2 mm Hg). Vehicle or Gen 2.5 ASO chemerin (25 mg/kg, sc) were then given once a week for four weeks. Gen 2.5 ASO chemerin caused a slowly developing but significant reduction in BP in control rats (-14.0±2.7 mm Hg) that was not significantly different from the BP fall in HF rats (-12.4±2.3 mm Hg). RT-PCR analyses validated complete loss of chemerin mRNA in the liver and fat (primary producers of chemerin) from rats given the Gen 2.5 ASO chemerin vs control. These data show that in normal, normotensive rats a HF diet alone is insufficient to increase BP dependence on chemerin