Abstract 078: Chemerin Antisense Oligonucleotide Lowers Blood Pressure in a Rat Model of Adiposity-Associated Hypertension.

Abstract

Chemerin is an adipokine, produced in liver and white adipose, whose human plasma levels have been positively associated with hypertension and obesity. In Sprague Dawley rats with normal adiposity and blood pressure (MAP), knockdown of chemerin throughout the body by antisense oligonucleotides (ASO) chronically reduced MAP by ~ 7 mmHg. Thus, we hypothesized that in high-fat-fed animals with hypertension and more visceral white adipose tissue, chemerin ASO would cause a greater reduction of blood pressure. Dahl salt-sensitive rats were fed a high fat diet (60% calories from fat) for 24 weeks after weaning. Radiotelemeters then were implanted for measuring MAP, temperature, heart rate and activity. After recovery and a one-week baseline recording period, animals received subcutaneous injections of either chemerin ASO (25 mg/kg) or scrambled control ASO (25 mg/kg) on days 0, 7, 14, 19. On day 21 the animals were euthanized for tissue and plasma analyses (chemerin PCR and Western). When compared to animals receiving scrambled control ASO, chemerin mRNA expression in animals receiving chemerin ASO was reduced by 99.5 ± 0.1% in liver, 90.6 ± 0.6% in mesenteric perivascular adipose tissue, and 99.3 ± 0.2% in retroperitoneal fat. Chemerin protein was undetectable in plasma from animals receiving chemerin ASO. MAP in rats receiving control ASO did not deviate significantly from baseline (179 ± 3 mmHg), while MAP in rats receiving chemerin ASO dropped by 32 ± 2 mmHg after four injections without a significant change in heart rate (abstract figure). These data support the involvement of chemerin in adiposity-associated hypertension and suggest a possible new approach to treating hypertension.