PMID- 10807734
OWN - NLM
STAT- MEDLINE
DCOM- 20000620
LR  - 20220311
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 20
IP  - 5
DP  - 2000 May
TI  - Simultaneously increased TxA(2) activity in isolated arterioles and platelets of 
      rats with hyperhomocysteinemia.
PG  - 1203-8
AB  - We aimed to elucidate the effect of hyperhomocysteinemia (HHcy) on the synthesis 
      of prostaglandins in rat skeletal muscle arterioles and platelets. Male Wistar 
      rats were divided into 2 groups: (1) control rats, with plasma Hcy levels of 
      6.5+/-0.5 micromol/L (n=50) and (2) rats with HHcy, induced by daily intake of 1 
      g/kg body weight methionine in the drinking water for 4 weeks (plasma Hcy levels 
      were 20.6+/-3.0 micromol/L, P<0.01 versus controls; n=50). Arterioles (diameter 
      approximately 130 micrometer) were isolated from the gracilis muscle, cannulated, 
      and pressurized (at 80 mm Hg), and changes in their diameters were followed by 
      video microscopy. Constrictions to bradykinin (BK; 10(-10) to 10(-7) mol/L) were 
      significantly greater in HHcy than in control rat arterioles (at 10(-9) mol/L BK, 
      changes were 11+/-3% in control and 41+/-9% in HHcy rats). The cyclooxygenase 
      inhibitor indomethacin (10(-5) mol/L), the prostaglandin H(2)/thromboxane A(2) 
      (PGH(2)/TxA(2)) receptor antagonist SQ 29,548 (10(-6) mol/L), or the TxA(2) 
      synthase inhibitor furegrelate (5x10(-6) mol/L) significantly decreased 
      constrictions to BK in both groups but more so in HHcy arterioles, thus 
      eliminating the difference between responses of HHcy and control arterioles. 
      Constrictions to U46619 (a TxA(2) analogue) were significantly greater in HHcy 
      than in control arterioles (at 10(-8) mol/L U46619, values for controls were 
      33+/-2% and 54+/-3% for HHcy). Endothelium removal or indomethacin treatment 
      attenuated constrictions to U46619 in HHcy arterioles and eliminated the 
      difference in responses. Also, aggregation of platelets from HHcy rats to 
      collagen and ADP was significantly enhanced compared with controls (with 5 
      microgram/mL collagen: controls, 23+/-5%; HHcy, 49+/-5%; with 10(-7) mol/L ADP: 
      controls, 25+/-3%; HHcy, 35+/-3%). Indomethacin or SQ 29,548 caused greater 
      inhibition of aggregation of HHcy platelets compared with controls, thereby 
      eliminating the differences between the 2 groups. Thus, HHcy enhances TxA(2) 
      synthesis both in the arteriolar endothelium and platelets. By promoting vascular 
      constriction and platelet aggregation simultaneously, these alterations are 
      likely to contribute to the atherothrombotic vascular diseases described in HHcy.
FAU - Ungvari, Z
AU  - Ungvari Z
AD  - Institute of Pathophysiology, Semmelweis University of Medicine, Budapest, 
      Hungary.
FAU - Sarkadi-Nagy, E
AU  - Sarkadi-Nagy E
FAU - Bagi, Z
AU  - Bagi Z
FAU - Szollar, L
AU  - Szollar L
FAU - Koller, A
AU  - Koller A
LA  - eng
GR  - HL-46813/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  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Fatty Acids)
RN  - 0 (Vasoconstrictor Agents)
RN  - 57576-52-0 (Thromboxane A2)
RN  - 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid)
RN  - 9007-34-5 (Collagen)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology
MH  - Animals
MH  - Arterioles/drug effects/pathology/*physiology
MH  - Blood Platelets/*metabolism
MH  - Blood Pressure
MH  - Bradykinin/pharmacology
MH  - Collagen/pharmacology
MH  - Fatty Acids/blood
MH  - Hyperhomocysteinemia/blood/*metabolism/pathology
MH  - Lipid Peroxidation
MH  - Male
MH  - Platelet Aggregation/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Thromboxane A2/*metabolism
MH  - Vasoconstriction/drug effects
MH  - Vasoconstrictor Agents/pharmacology
EDAT- 2000/05/16 09:00
MHDA- 2000/06/24 11:00
CRDT- 2000/05/16 09:00
PHST- 2000/05/16 09:00 [pubmed]
PHST- 2000/06/24 11:00 [medline]
PHST- 2000/05/16 09:00 [entrez]
AID - 10.1161/01.atv.20.5.1203 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2000 May;20(5):1203-8. doi: 
      10.1161/01.atv.20.5.1203.