A deficiency in the formation of 20‐HETE impairs the myogenic and TGF responses of the Af‐Art of Dahl salt sensitive rats (857.8)

Previously, we demonstrated that transfer of chromosome 5 containing the CYP4A genes from Brown Norway (BN) rat onto the Dahl S (SS) genetic background (SS.5 BN strain) increases the formation of 20‐HETE in renal microvessels and contributes to the antihypertensive effect. Therefore, we hypothesize that a deficiency in the formation of 20‐HETE in the renal vasculature impairs myogenic and TGF responses in the afferent arteriole (Af‐Art) in SS rats. The production of 20‐HETE was 54% lower in renal microvessels of SS rats than in SS.5 BN rats. The luminal diameter of the Af‐Art decreased by 15±2% (n=6, p<0.05) in SS.5 BN rats when the perfusion pressure was increased from 60 to 120 mmHg, whereas it remained unaltered in SS rats. Administration of an adenosine type 1 receptor agonist (CCPA, 1 µM) reduced the diameter of the Af‐Art in the SS.5 BN rats by 44±2%(n=6, p<0.05)., whereas the Af‐Art of SS rats was unaltered SS rats exhibited poor autoregulation of RBF and P GC in vivo, whereas they were well regulated in SS.5 BN rats. Administration of a 20‐HETE synthesis inhibitor, HET0016 (1 µM, n=6) completely blocked the myogenic and adenosine responses in the Af‐Art and autoregulation of RBF and P GC in SS.5 BN rats but not in SS rats. These data indicated that a deficiency in the formation of 20‐HETE in renal microvessels contributes to the lack of renal autoregulation and development of hypertension in SS rats. Grant Funding Source : This studies were supported by Grant HL36279 and AHA 13POST14220024.