PMID- 3413813
OWN - NLM
STAT- MEDLINE
DCOM- 19881012
LR  - 20190727
IS  - 0039-2499 (Print)
IS  - 0039-2499 (Linking)
VI  - 19
IP  - 9
DP  - 1988 Sep
TI  - Thromboxane A2 in severe hypertension and stroke in stroke-prone spontaneously 
      hypertensive rats.
PG  - 1145-50
AB  - Thromboxane A2 is a prostanoid having potent platelet aggregatory and 
      vasoconstrictor properties. To determine a possible role for thromboxane A2 in 
      the development of severe hypertension and stroke, we chronically administered 
      the selective thromboxane A2 synthase inhibitor UK-38,485 (Dazmegrel) to 
      stroke-prone spontaneously hypertensive rats (SHRSP). Serum thromboxane B2 (the 
      stable hydrolysis product of thromboxane A2) generation was significantly greater 
      in incubates of whole blood from SHRSP than in those from normotensive control 
      Wistar-Kyoto rats and was inhibited greater than 89% by UK-38,485 administered in 
      vivo. In 10 male SHRSP fed a Japanese-style rat chow and given 1% NaCl in 
      drinking water to accelerate the occurrence of stroke, treatment with 100 
      mg/kg/day UK-38,485 by gavage starting at 8.6 weeks of age diminished systolic 
      blood pressure elevation at 10 (205 +/- 2 vs. 220 +/- 4 mm Hg, p less than 0.01) 
      and 11 weeks of age (210 +/- 4 vs. 239 +/- 7 mm Hg, p less than 0.01) compared 
      with 10 untreated SHRSP. The ultimate establishment of severe hypertension was 
      not prevented by UK-38,485. Stroke-related mortality was 70% in both 
      UK-38,485-treated and control SHRSP at 14 weeks of age. Histologic examination 
      revealed cerebrovascular lesions consistent with the occurrence of stroke in both 
      control and UK-38,485-treated SHRSP. Our results support a possible role for 
      thromboxane A2 in the elevation of blood pressure in SHRSP but do not support a 
      possible role for the prevention of stroke by thromboxane A2 synthase inhibition 
      in these rats.
FAU - Stier, C T Jr
AU  - Stier CT Jr
AD  - Department of Pharmacology, New York Medical College, Valhalla 10595.
FAU - Benter, I F
AU  - Benter IF
FAU - Levine, S
AU  - Levine S
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  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Imidazoles)
RN  - 31340R8PVU (dazmegrel)
RN  - 54397-85-2 (Thromboxane B2)
RN  - 57576-52-0 (Thromboxane A2)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Brain/pathology
MH  - Cerebrovascular Disorders/chemically induced/*etiology/mortality/pathology
MH  - Disease Susceptibility
MH  - Hypertension/*etiology
MH  - Imidazoles/pharmacology
MH  - Male
MH  - Osmolar Concentration
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Thromboxane A2/*physiology
MH  - Thromboxane B2/blood
EDAT- 1988/09/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1988/09/01 00:00
PHST- 1988/09/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1988/09/01 00:00 [entrez]
AID - 10.1161/01.str.19.9.1145 [doi]
PST - ppublish
SO  - Stroke. 1988 Sep;19(9):1145-50. doi: 10.1161/01.str.19.9.1145.