Hypotensive effects of the lipoxygenase inhibitor phenidone in two-kidney, one clip Goldblatt hypertension.
This study examined the role of the lipoxygenase (LO) pathway in the maintenance of hypertension in rats with two-kidney, one clip (2K,1C) Goldblatt hypertension. A single dose of the lipoxygenase blocker phenidone was injected intraperitoneally to 2K,1C rats during the early phase (14 days) of the development of hypertension (mean intraarterial blood pressure 137 +/- 3.9 mm Hg). Phenidone (60 mg/kg) markedly decreased arterial pressure to nadir levels of 58.9% of resting blood pressure. The maximal changes were observed 15 min after injection and the hypotensive response was sustained for at least 2 h. Plasma renin concentration (PRC) increased from 74.3 +/- 18.9 to 281.0 +/- 6.5 ng/mL/h after injection (P less than .05). Thus, the hypotensive effect of phenidone was not due to suppression of renin secretion but presumably due to inhibition of its effects. It is suggested that arachidonate metabolites of the LO pathway at the vascular bed may be involved in maintenance of high arterial pressure in 2K,1C renovascular hypertension in rat.
Nozawa
K
K
Division of Endocrinology, Sepulveda Veterans Administration Medical Center, California.
Tuck
M L
ML
Golub
M
M
Eggena
P
P
Nadler
J
J
Stern
N
N
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D016859:Lipoxygenase Inhibitors; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D001095:Arachidonic Acids; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D016718:Arachidonic Acid; D012083:Renin; C015429:phenidone