Arachidonate CYP hydroxylases of kidney contribute to formation of hypertension and maintenance of blood pressure.
OBJECTIVE
To investigate the relationship of kidney-specific expression of cytochrome P-450 (CYP) 4A1 and the blood pressure.


METHODS
The specific sense and antisense CYP4A1 cDNA was administered respectively with the help of eukaryotic expression vector pcDNA3.1 to the Sprague-Dawley (SD) rats via sublingual vein (2 mg/kg). The systolic blood pressure of rats was assessed by the tail- cuff method, and the relative tissue expression of CYP4A1 was analyzed by Western blot and Northern blot at RNA and protein levels in the brain, heart, lung, liver, and kidney of control, sense, and anti-sense CYP4A1 cDNA-treated rats.


RESULTS
Two weeks after the injection of the sense and antisense CYP4A1 cDNA recombinants respectively, the mean systolic pressure of the transgenic rats increased by 1.8 kPa +/- 0.3 kPa (13.2 mmHg +/- 2.5 mmHg) or decreased by 1.7 kPa +/- 0.3 kPa (13.0 mmHg +/- 2.2 mmHg) compared with control. At the levels of transcription and translation, the Northern and Western blots all demonstrated that CYP4A1 preferentially overexpressed in the kidney.


CONCLUSIONS
The administration of sense and antisense CYP4A1 cDNA induced hypertension and hypotension, respectively, which indicated that renal arachidonate hydroxylase contributed to the formation of hypertension and maintenance of blood pressure in normotensive rats.
Zhang
Fan
F
Department of Internal Medicine and Gene Therapy Center, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Qian
Jia-Qing
JQ
Wang
Dao-Wen
DW
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003001:Cloning, Molecular; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000502:physiology*; D000072470:Cytochrome P450 Family 4; D016373:DNA, Antisense / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000201:enzymology* / Q000502:physiology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism / Q000502:physiology; D014442:Monophenol Monooxygenase; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014162:Transfection
C465387:Cyp4a1protein, rat; D065607:Cytochrome P-450 Enzyme Inhibitors; D016373:DNA, Antisense; D006893:Hydroxyeicosatetraenoic Acids; D012333:RNA, Messenger; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000072470:Cytochrome P450 Family 4; D014442:Monophenol Monooxygenase