PMID- 20667508
OWN - NLM
STAT- MEDLINE
DCOM- 20110314
LR  - 20161125
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 62
IP  - 5
DP  - 2010 Nov
TI  - Induction of hemeoxygenase-1 attenuates the hypertension and renal inflammation 
      in spontaneously hypertensive rats.
PG  - 400-7
LID - 10.1016/j.phrs.2010.07.005 [doi]
AB  - The reno-protective mechanisms of hemeoxygenase-1 (HO-1) induction in 
      hypertension remain unclear. We hypothesize that induction of HO-1 will decrease 
      blood pressure and proteinuria with a marked decrease in oxidative stress and 
      inflammation in spontaneously hypertensive rats (SHR). Male Wistar Kyoto (WKY) 
      and SHR were injected with the HO-1 inducer cobalt protoporphyrin (CoPP, 1.5 
      mg/kgs.c. twice weekly) which resulted in an increase in renal HO-1 expression 
      after 2 weeks. CoPP reduced mean arterial pressure (133+/-2 mmHg vs. 144+/-4 mmHg, 
      p<0.05) and proteinuria (14+/-1 mg/day vs. 24+/-2 mg/day, p<0.05) in SHR as compared 
      to baseline values, with no effect in WKY. Renal cortical superoxide (O(2)(-)) 
      production and urinary 8-isoprostane excretion were higher in SHR compared to WKY 
      (O(2)(-): 11+/-1 CPM/mug vs. 6+/-1 CPM/mug protein, p<0.05; 8-iso: 7+/-1 ng/day vs. 3+/-0.8 
      ng/day, p<0.05) and CoPP attenuated oxidative stress levels only in SHR (O(2)(-): 
      5+/-1 CPM/mug, p<0.05; 8-isoprostane: 4+/-0.7 ng/day) without an overall effect on 
      antioxidant defense enzymes expression and activities. SHR showed a marked 
      elevation in plasma C-reactive protein (CRP) and urinary monocyte chemoattractant 
      protein-1 (MCP-1) excretion compared with WKY and HO-1 induction reduced the CRP 
      and MCP-1 levels in SHR. Cortical COX2 expression and urinary thromboxane B(2) 
      (TXB(2)) excretion were also significantly elevated in SHR compared to WKY and 
      levels were reduced with induction of HO-1. Inhibition of HO with stannous 
      mesoporphyrin further increased blood pressure and proteinuria in SHR and blocked 
      the ability of CoPP to reduce blood pressure and proteinuria in SHR. These data 
      demonstrate that induction of HO-1 slows the progression of hypertension and 
      proteinuria in SHR and these changes were associated with reduced renal oxidative 
      stress and inflammation.
CI  - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
FAU - Elmarakby, Ahmed A
AU  - Elmarakby AA
AD  - Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, United 
      States. aelmarakby@mcg.edu
FAU - Faulkner, Jessica
AU  - Faulkner J
FAU - Posey, Sam P
AU  - Posey SP
FAU - Sullivan, Jennifer C
AU  - Sullivan JC
LA  - eng
PT  - Journal Article
DEP - 20100805
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Antioxidants)
RN  - 0 (Metalloporphyrins)
RN  - 0 (Protoporphyrins)
RN  - 0 (stannous mesoporphyrin)
RN  - 11062-77-4 (Superoxides)
RN  - 63AAN3JDZE (cobaltiprotoporphyrin)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Blood Pressure/drug effects/physiology
MH  - Catalase/metabolism
MH  - Enzyme Induction
MH  - Heme Oxygenase-1/antagonists & inhibitors/*metabolism
MH  - Hypertension/drug therapy/enzymology/*physiopathology
MH  - Inflammation/*drug therapy
MH  - Kidney/metabolism/*physiopathology
MH  - Male
MH  - Metalloporphyrins/administration & dosage/pharmacology
MH  - Oxidative Stress/drug effects
MH  - Protoporphyrins/administration & dosage/*pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Superoxide Dismutase/metabolism
MH  - Superoxides/metabolism/pharmacology
EDAT- 2010/07/30 06:00
MHDA- 2011/03/15 06:00
CRDT- 2010/07/30 06:00
PHST- 2010/03/18 00:00 [received]
PHST- 2010/07/19 00:00 [revised]
PHST- 2010/07/20 00:00 [accepted]
PHST- 2010/07/30 06:00 [entrez]
PHST- 2010/07/30 06:00 [pubmed]
PHST- 2011/03/15 06:00 [medline]
AID - S1043-6618(10)00155-6 [pii]
AID - 10.1016/j.phrs.2010.07.005 [doi]
PST - ppublish
SO  - Pharmacol Res. 2010 Nov;62(5):400-7. doi: 10.1016/j.phrs.2010.07.005. Epub 2010 
      Aug 5.