PMID- 10446068
OWN - NLM
STAT- MEDLINE
DCOM- 19990824
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 19
IP  - 8
DP  - 1999 Aug
TI  - Dysfunction of nitric oxide mediation in isolated rat arterioles with methionine 
      diet-induced hyperhomocysteinemia.
PG  - 1899-904
AB  - In humans, increased plasma homocysteine (Hcy) has been shown to be correlated 
      with occlusive arterial diseases and atherosclerosis. Studies of isolated 
      conductance vessels of experimental animals suggest that Hcy may interfere with 
      local vasoregulatory mechanisms, yet the effect of hyperhomocysteinemia (HHcy) on 
      the function of microvessels, such as skeletal muscle arterioles, has not been 
      investigated. Male Wistar rats were divided into 2 groups: control rats (C; 
      plasma Hcy, 7.1+/-0.3 micromol/L; n=25), and rats made HHcy by 1 g/kg body weight 
      daily intake of methionine in the drinking water for 4 weeks (plasma Hcy, 
      23.6+/-2.9 micromol/L; P<0.01 versus C; n=25). First-order arterioles ( 
      approximately 130 micrometer in diameter) were isolated from gracilis muscle, 
      cannulated, and pressurized (80 mm Hg, no-flow conditions). Changes in diameter 
      were observed by videomicroscopy. Arteriolar constrictions to norepinephrine (NE; 
      3x10(-7) mol/L) were significantly (P<0.01) greater in HHcy compared with C rats 
      (C, 37.7+/-4.9%; HHcy, 59.5+/-5. 2%). Removal of the endothelium (-E) augmented 
      NE-induced constrictions only in arterioles from C rats, whereas it had no effect 
      on responses of arterioles from HHcy rats (C-E, 55.9+/-6.9%; HHcy-E, 
      56.5+/-7.0%). Dilations to cumulative doses of acetylcholine (ACh; 10(-8) mol/L) 
      were significantly reduced in arterioles from HHcy rats (C, 64.0+/-5.2%; HHcy, 
      24.1+/-6.8%). Inhibition of nitric oxide (NO) synthesis with 
      N(omega)-nitro-L-arginine (L-NNA; 10(-4) mol/L) significantly decreased 
      ACh-induced dilations of C arterioles, whereas it did not affect HHcy arterioles. 
      Similar alterations were found in arteriolar dilations to histamine, another 
      known NO-dependent agonist. Endothelium-independent dilations to the NO donor 
      sodium nitroprusside were not different in arterioles from C and HHcy rats, 
      either in the presence or absence of L-NNA. Presence of superoxide dismutase and 
      catalase (scavenger of reactive oxygen metabolites) did not affect HHcy-induced 
      alterations in the ACh response. We conclude that hyperhomocysteinemia reduces 
      rat skeletal muscle arteriolar dilations in response to ACh and histamine, and 
      enhances constrictions to NE, alterations that are likely to be caused by the 
      reduced mediation of these responses by NO. The reduced activity of NO in 
      arterioles may contribute to the microvascular impairment described in HHcy.
FAU - Ungvari, Z
AU  - Ungvari Z
AD  - Department of Pathophysiology, Semmelweis University of Medicine, H-1445, 
      Budapest, Hungary.
FAU - Pacher, P
AU  - Pacher P
FAU - Rischak, K
AU  - Rischak K
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 (Vasodilator Agents)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 820484N8I3 (Histamine)
RN  - AE28F7PNPL (Methionine)
RN  - N9YNS0M02X (Acetylcholine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Arterioles/drug effects/*metabolism/physiology
MH  - Arteriosclerosis/physiopathology
MH  - Diet
MH  - Histamine/pharmacology
MH  - Homocysteine/*blood
MH  - In Vitro Techniques
MH  - Male
MH  - Methionine/*administration & dosage
MH  - Nitric Oxide/*physiology
MH  - Nitroprusside/pharmacology
MH  - Norepinephrine/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Vascular Resistance/drug effects
MH  - Vasodilator Agents/pharmacology
EDAT- 1999/08/14 00:00
MHDA- 1999/08/14 00:01
CRDT- 1999/08/14 00:00
PHST- 1999/08/14 00:00 [pubmed]
PHST- 1999/08/14 00:01 [medline]
PHST- 1999/08/14 00:00 [entrez]
AID - 10.1161/01.atv.19.8.1899 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1999 Aug;19(8):1899-904. doi: 
      10.1161/01.atv.19.8.1899.