Kidney-specific induction of heme oxygenase-1 prevents angiotensin II hypertension.
The main goal of this study was to determine whether kidney-specific induction of heme oxygenase-1 (HO-1) can prevent the development of angiotensin (Ang) II-dependent hypertension. To test this hypothesis, intrarenal medullary interstitial catheters were implanted into the left kidney of uninephrectomized mice. Infusion of cobalt protoporphyrin (CoPP; 250 microg/mL; at 50 microL/h for 48 hours) resulted in significant induction of HO-1 in the renal medulla when examined 2 weeks after the infusion with no induction observed in other organs, such as the heart or liver. Next, we examined the effect of renal-specific induction of HO-1 on the development of Ang II-dependent hypertension. CoPP or vehicle (0.1 mol/L NaOH [pH 8.3]) was infused as indicated above 2 days before implantation of an osmotic minipump, which delivered Ang II or saline vehicle at a rate of 1 microg/kg per minute. Mean arterial pressure was measured in conscious, unrestrained mice for 3 consecutive days starting on day 7 after implantation of the minipumps. Mean arterial pressure averaged 114+/-5, 122+/-4, 162+/-2, and 125+/-6 mm Hg in vehicle-, intrarenal medullary interstitial CoPP-, Ang II-, and Ang II + intrarenal medullary interstitial CoPP-treated mice, respectively (n=6 or 7). These results demonstrate that kidney-specific induction of HO-1 prevents the development of Ang II-dependent hypertension and that induction of HO-1 in the kidney may be the mechanism by which systemic delivery of CoPP lowers blood pressure in Ang II-dependent hypertension.
Vera
Trinity
T
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Kelsen
Silvia
S
Stec
David E
DE
D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D004195:Disease Models, Animal; D004790:Enzyme Induction; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007260:Infusion Pumps; D007679:Kidney Medulla / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011524:Protoporphyrins / Q000008:administration & dosage*; D013053:Spectrophotometry; D016896:Treatment Outcome
D011524:Protoporphyrins; D000804:Angiotensin II; D006418:Heme; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1