Role of 20-HETE in the impaired myogenic and TGF responses of the Af-Art of Dahl salt-sensitive rats.

Abstract

The present study examined whether 20-HETE production is reduced in the renal vasculature and whether this impairs myogenic or tubuloglomerular feedback (TGF) responses of the afferent arteriole (Af-Art). The production of 20-HETE was 73% lower in renal microvessels of Dahl salt-sensitive rats (SS) rats than in SS.5(BN) rats, in which chromosome 5 from the Brown Norway (BN) rat containing the CYP4A genes was transferred into the SS genetic background. The luminal diameter of the Af-Art decreased by 14.7 ± 1.5% in SS.5(BN) rats when the perfusion pressure was increased from 60 to 120 mmHg, but 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%, whereas the diameter of the Af-Art of SS rats was unaltered. Autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) was significantly impaired in SS rats but was intact in SS.5(BN) rats. Administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM), completely blocked the myogenic and adenosine responses in the Af-Art and autoregulation of RBF and PGC in SS.5(BN) rats, but it had no effect in SS rats. These data indicate that a deficiency in the formation of 20-HETE in renal microvessels impairs the reactivity of the Af-Art of SS rats and likely contributes to the development of hypertension induced renal injury.

• Authors: Ying Ge, Sydney R Murphy, Fan Fan, Jan Michael Williams, John R Falck, Ruisheng Liu, Richard J Roman
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 307 Issue 5 Pg. F509-15 (Sep 01 2014) ISSN: 1522-1466 [Electronic] United States
• PMID: 25007877 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Hydroxyeicosatetraenoic Acids
• Arachidonic Acid
• Transforming Growth Factors
• 20-hydroxy-5,8,11,14-eicosatetraenoic acid
• Adenosine

Topics

• Adenosine (pharmacology)
• Afferent Pathways (physiopathology)
• Animals
• Arachidonic Acid (metabolism)
• Arterioles (physiopathology)
• Disease Models, Animal
• Hydroxyeicosatetraenoic Acids (physiology)
• Hypertension (metabolism, physiopathology)
• Kidney (blood supply, physiopathology)
• Male
• Microvessels (physiopathology)
• Muscle Development (physiology)
• Rats
• Rats, Inbred BN
• Rats, Inbred Dahl
• Rats, Sprague-Dawley
• Regional Blood Flow (drug effects)
• Transforming Growth Factors (physiology)
• Vasoconstriction (drug effects)