Cytochrome P450 content and activities are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared with those of normotensive, Wistar-Kyoto (WKY), control rats during the period of rapid elevation of blood pressure. We studied the effect of
heme arginate, a potent inducer of
heme oxygenase (EC 1.14.99.3), on microsomal
cytochrome P450 levels and activities and blood pressure in SHR at 7 wk of age. Administration of
heme arginate (15 mg/kg
body weight for 4 d) resulted in a marked decrease in blood pressure from 156.3 +/- 4.7 to 129.8 +/- 4.5 mm Hg (P less than 0.001), whereas blood pressure in SHR receiving the vehicle control was not affected. The blood pressure of age-matched WKY was not affected by
heme arginate.
Heme oxygenase activity increased in both hepatic and renal microsomes of SHR and WKY by two- to four-fold
after treatment with
heme arginate. Maximal increase of
heme oxygenase mRNA occurred 5-7 h after the last injection of
heme arginate and returned to control levels after 24 h. The increase in
heme oxygenase activity was associated with a parallel decrease in
cytochrome P450 content and in the activity of
cytochrome P450 omega/omega-1 arachidonate
hydroxylases in kidneys of SHR. It is postulated that
heme arginate treatment resulted in induction of
heme oxygenase which consequently led to a diminution of
cytochrome P450, especially the arachidonate omega/omega-1
hydroxylases leading to a marked decrease in 19-hydroxyeicosatetraenoic
acid (
HETE) and
20-HETE. The effect of
heme arginate on blood pressure may be mediated via these biochemical events inasmuch as both
19-HETE and
20-HETE produced by the kidney may promote
hypertension by causing vasoconstriction and
sodium retention.