PMID- 1550666
OWN - NLM
STAT- MEDLINE
DCOM- 19920429
LR  - 20190509
IS  - 0895-7061 (Print)
IS  - 0895-7061 (Linking)
VI  - 5
IP  - 2
DP  - 1992 Feb
TI  - The lipoxygenase inhibitor phenidone protects against proteinuria and stroke in 
      stroke-prone spontaneously hypertensive rats.
PG  - 56-63
AB  - The present study examined whether the dual cyclooxygenase/lipoxygenase inhibitor 
      phenidone would protect stroke-prone spontaneously hypertensive rats (SHRSP) from 
      stroke and hypertensive renal disease. Vehicle-treated SHRSP (N = 6), fed 
      stroke-prone rodent diet and 1% saline, exhibited severe systolic blood pressure 
      elevation (261 +/- 10 mm Hg, mean +/- SEM), marked proteinuria (90 +/- 12 
      mg/day), and stroke, with an average age at death of 14 +/- 1 weeks. In a second 
      group of six saline-loaded SHRSP, treatment with phenidone (60 mg/kg/day) was 
      started at 8.4 weeks of age. Despite establishment of severe hypertension in this 
      group (274 +/- 10 mm Hg), proteinuria remained at basal levels (28 +/- 13 
      mg/day), and signs of stroke were absent (P less than .01 v vehicle) through at 
      least 16 weeks of age. Phenidone treatment also prevented the declines in body 
      weight and food intake observed in vehicle-treated SHRSP, and maintained urine 
      volume and saline intake. Serum 12-hydroxy-eicosatetraenoic acid (12-HETE) 
      generation was significantly inhibited greater than 50% in incubates of whole 
      blood from phenidone-treated SHRSP. We have previously shown that agents which 
      interfere with the renin-angiotensin system afford protection from renal and 
      cerebrovascular injury in saline-loaded SHRSP; cyclooxygenase inhibition alone 
      will hasten the onset of these pathologic changes. Whether phenidone, which has 
      been reported to attenuate angiotensin II-mediated effects, affords vascular 
      protection by interference with a lipoxygenase-mediated action of angiotensin II 
      remains to be elucidated.
FAU - Munsiff, A V
AU  - Munsiff AV
AD  - Department of Pharmacology, New York Medical College, Valhalla 10595.
FAU - Chander, P N
AU  - Chander PN
FAU - Levine, S
AU  - Levine S
FAU - Stier, C T Jr
AU  - Stier CT Jr
LA  - eng
GR  - HL-35522/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hypertens
JT  - American journal of hypertension
JID - 8803676
RN  - 0 (Eicosanoids)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (Pharmaceutical Vehicles)
RN  - 0 (Pyrazoles)
RN  - H0U5612P6K (phenidone)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Cerebrovascular Disorders/*prevention & control
MH  - Eicosanoids/blood
MH  - Kidney/drug effects/pathology
MH  - Lipoxygenase Inhibitors/*pharmacology
MH  - Pharmaceutical Vehicles
MH  - Proteinuria/*prevention & control
MH  - Pyrazoles/*therapeutic use
MH  - Rats
MH  - Rats, Inbred SHR
EDAT- 1992/02/11 19:15
MHDA- 2001/03/28 10:01
CRDT- 1992/02/11 19:15
PHST- 1992/02/11 19:15 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1992/02/11 19:15 [entrez]
AID - 10.1093/ajh/5.2.56 [doi]
PST - ppublish
SO  - Am J Hypertens. 1992 Feb;5(2):56-63. doi: 10.1093/ajh/5.2.56.