Arachidonate CYP hydroxylases of kidney contribute to formation of hypertension and maintenance of blood pressure.

AIM: 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.
CONCLUSION: 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.