Increased renal vascular reactivity to ANG II after unilateral nephrectomy in the rat involves 20-HETE

1 Service de Physiologie et de Pharmacologie and 3 Service de Biochimie, Université de Mons-Hainaut, Mons, 2 Département de Physiologie et Pharmacologie, Facultés Universitaires Notre Dame de la Paix, Namur, Belgium, and 4 Vascular Biology Center, Medical College of Georgia, Augusta, Georgia Submitted 6 June 2005 ; accepted in final form 25 April 2006 This study examined the role of intrarenal ANG II in the renal vascular reactivity changes occurring in the remaining kidney undergoing adaptation following contralateral nephrectomy. Renal blood flow responses to intrarenal injections of ANG II (0.25 to 5 ng) were measured in anesthetized euvolemic male Wistar rats 1, 4, 12, and 24 wk after uninephrectomy (UNX) or sham procedure (SHAM). At week 4 , renal vasoconstriction induced by 2 ng ANG II was greater in UNX (69 ± 5%) than in SHAM rats (50 ± 3%; P < 0.01). This response was inhibited, by 50 and 66%, and by 20 and 25%, in SHAM and UNX rats, after combined injections of ANG II and losartan, or PD-123319 ( P < 0.05), respectively. Characteristics of ANG II receptor binding in isolated preglomerular resistance vessels were similar in the two groups. After prostanoid inhibition with indomethacin, renal vasoconstriction was enhanced by 42 ± 8% ( P < 0.05), only in SHAM rats, whereas after 20-HETE inhibition with HET0016, it was reduced by 53 ± 16% ( P < 0.05), only in UNX rats. These differences vanished after concomitant prostanoid and 20-HETE inhibition in the two groups. After UNX, renal cortical protein expression of cytochrome P-450 2c23 isoform (CYP2c23) and cyclooxygenase-1 (COX-1) was unaltered, but it was decreased for CYP4a and increased for COX-2. In conclusion, renal vascular reactivity to ANG II was significantly increased in the postuninephrectomy adapted kidney, independently of protein expression, but presumably involving interactions between 20-HETE and COX in the renal microvasculature and changes in the paracrine activity of ANG II and 20-HETE. adapted kidney; renal blood flow; eicosanoids; indomethacin; HET0016 Address for reprint requests and other correspondence: R. Kramp, Service de Physiologie et Pharmacologie, Faculté de Médecine et Pharmacie, Université de Mons-Hainaut, 6, Ave. du Champ de Mars "Le Pentagone", B-7000 MONS, Belgium (e-mail: ronald.kramp{at}umh.ac.be )