Submitted on June 6, 2005
Accepted on April 25, 2006
Increased renal vascular reactivity to angiotensin II after
unilateral nephrectomy in the rat involves 20-HETE
Emma Joly1, Rachid Seqqat1, Bruno Flamion2, Nathalie Caron1, Alain Michel3, John D Imig4, and Ronald Kramp1*
1 Physiology and Pharmacology, University of Mons-Hainaut, Mons, Belgium
2 Physiology and Pharmacology, University of Namur, Namur, Belgium
3 Biological Chemistry, University of Mons-Hainaut, Mons, Belgium
4 Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, United States
* To whom correspondence should be addressed. E-mail: ronald.kramp{at}umh.ac.be.
This study examined the role of intrarenal angiotensin II (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 anaesthetized euvolaemic male Wistar rats 1, 4, 12 and 24 weeks following 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, while 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 CYP2c23 and 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 post-uninephrectomy 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.
