M A Carroll1, R Kemp, M K Cheng, J C McGiff. 1. Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA. mailread_carroll@nymc.edu
Abstract
BACKGROUND: 20-hydroxyeicosatetraenoic acid (20-HETE) is the preeminent renal eicosanoid. The protean properties of 20-HETE - vasoactivity, mitogenicity and modulation of transport in key nephron segments - serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and electrolyte excretion and as a second messenger for endothelin-1 (ET-1) and a mediator of selective renal effects of angiotensin II (AII). Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular microvessels, particularly afferent arterioles. METHODS AND RESULTS: We had reported that rat preglomerular microvessels (PGMV; afferent-interlobular-arcuate/interlobular) in response to angiotensin II (AII) generate primarily 20-HETE and lesser quantities of 19-HETE. We have now addressed a possible link between the renin-angiotensin-system (RAS) and induction of cyclooxygenase (COX-2). As Na+ deprivation induces COX-2 expression/activity in the renal cortex and AII stimulates release of 20-HETE from PGMV, we used a stimulus, low dietary salt, to activate the RAS and COX-2 and thereby explore potential interactions involving 20-HETE and COX-2. CONCLUSIONS: The capacity of COX to metabolize 20-HETE to prostaglandin analogs e.g., 20-OH PGF2a and 20-OH PGE2, may be critical to modifying the renal vascular and tubular actions of the eicosanoids.
BACKGROUND:20-hydroxyeicosatetraenoic acid (20-HETE) is the preeminent renal eicosanoid. The protean properties of 20-HETE - vasoactivity, mitogenicity and modulation of transport in key nephron segments - serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and electrolyte excretion and as a second messenger for endothelin-1 (ET-1) and a mediator of selective renal effects of angiotensin II (AII). Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular microvessels, particularly afferent arterioles. METHODS AND RESULTS: We had reported that rat preglomerular microvessels (PGMV; afferent-interlobular-arcuate/interlobular) in response to angiotensin II (AII) generate primarily 20-HETE and lesser quantities of 19-HETE. We have now addressed a possible link between the renin-angiotensin-system (RAS) and induction of cyclooxygenase (COX-2). As Na+ deprivation induces COX-2 expression/activity in the renal cortex and AII stimulates release of 20-HETE from PGMV, we used a stimulus, low dietary salt, to activate the RAS and COX-2 and thereby explore potential interactions involving 20-HETE and COX-2. CONCLUSIONS: The capacity of COX to metabolize 20-HETE to prostaglandin analogs e.g., 20-OH PGF2a and 20-OH PGE2, may be critical to modifying the renal vascular and tubular actions of the eicosanoids.
Authors: L Hacein-Bey; D R Harder; H T Meier; P N Varelas; N Miyata; K K Lauer; J F Cusick; R J Roman Journal: AJNR Am J Neuroradiol Date: 2006 Jun-Jul Impact factor: 3.825
Authors: Fan Fan; Ying Ge; Wenshan Lv; Matthew R Elliott; Yoshikazu Muroya; Takashi Hirata; George W Booz; Richard J Roman Journal: Front Biosci (Landmark Ed) Date: 2016-06-01