title: The expression of heme oxygenase-1 and inducible nitric oxide synthase in aorta during the development of hypertension in spontaneously hypertensive rats.
abstract: BACKGROUND
  The aim of this study was to observe the time-course changes of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) induction in aorta during the development of hypertension, as well as the relationship of HO-1/carbon monoxide (CO) system and iNOS/nitric oxide (NO) system in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  The systolic blood pressure (SBP) was determined in conscious rats by the tail-cuff method. The tissue HO-1 and iNOS mRNA and protein levels were estimated with reverse transcription polymerase chain reaction and Western blot method.
  
  
  RESULTS
  The expression of HO-1 and iNOS in aorta increased with the SBP elevation during the development of SHR and was attenuated when the hypertension was lowered with the vasodilator hydralazine. At 8 weeks, only HO-1 was induced, whereas at 12 and 16 weeks, both HO-1 and iNOS were observed. The level of plasma nitrite/nitrate was associated with the change in iNOS expression in SHR. In addition, the SBP of 8-week-old SHR was significantly increased after pretreatment with zinc protoporphyrin IX for 7 consecutive days. Chronic blockade of iNOS activity by aminoguanidine resulted in significant up-regulation of HO-1, but the pressor effect was blunt.
  
  
  CONCLUSIONS
  These results suggest that the up-regulation of HO-1 and iNOS in aorta is a compensatory mechanism for the elevation of SBP during the development of hypertension in SHR. The expression of HO-1 is earlier than that of iNOS. Our data suggest that the HO-1/CO system takes over and acts as a major modulator for the regulation of SBP when the iNOS/NO system is suppressed.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Pao-Yun
authors.initials: PY
authors.lastname: Cheng
authors.forename: Jin-Jer
authors.initials: JJ
authors.lastname: Chen
authors.forename: Mao-Hsiung
authors.initials: MH
authors.lastname: Yen
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta / Q000201:enzymology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000187:drug effects; D009573:Nitrites / Q000097:blood; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006830:Hydralazine; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C004479:pimagedine