Treatment with tin prevents the development of hypertension in spontaneously hypertensive rats.
Cytochrome P-450-dependent metabolites of arachidonic acid (AA) increased in the kidneys of young, spontaneously hypertensive rats (SHRs) during the period of rapid elevation of blood pressure (BP) but not in adult SHRs or in Wistar Kyoto rats (WKYs) with normal BP. Treatment of SHRs and WKYs with stannous chloride (SnCl2), which selectively depletes renal cytochrome P-450, restored BP to normal, coincident with a natriuresis, in young but not in adult SHRs and did not affect either BP or sodium excretion in WKYs. Depletion of renal cytochrome P-450 was associated with decreased generation of these AA metabolites only in young SHRs. The antihypertensive effect of SnCl2 in young SHRs was greatly reduced by prevention of its cytochrome P-450-depleting action.
Sacerdoti
D
D
Department of Pharmacology, New York Medical College, Valhalla 10595.
Escalante
B
B
Abraham
N G
NG
McGiff
J C
JC
Levere
R D
RD
Schwartzman
M L
ML
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006973:Hypertension / Q000517:prevention & control*; D007668:Kidney / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D014001:Tin / Q000627:therapeutic use*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D003035:Cobalt; D014001:Tin; D003577:Cytochrome P-450 Enzyme System; D006419:Heme Oxygenase (Decyclizing)