Effects of hyperhomocysteinemia on arterial pressure and nitric oxide production in pregnant rats.
BACKGROUND
An elevated plasma level of homocysteine (hyperhomocysteinemia) is thought to be an important risk factor for a variety of cardiovascular diseases including preeclampsia. Although clinical studies have reported a two- to threefold elevation in plasma levels of homocysteine in women who developed preeclampsia, the importance of hyperhomocysteinemia in causing endothelial dysfunction and increases in arterial pressure during pregnancy is unknown.


METHODS
Therefore, the purpose of this study was to determine the effects of a two- to threefold elevation in plasma homocysteine levels on arterial pressure, chronic pressure-natriuresis relationship, and endothelial factors during pregnancy in the rat. Homocysteine treatment for 4 weeks increased plasma homocysteine levels in pregnant rats from 7.1 +/- 1.9 to 16.7 +/- 2.3 micromol/l.


RESULTS
Homocysteine treatment decreased urinary nitrate/nitrite levels from 53 +/- 7 vs. 39 +/- 5 (micromol/24 h/kg body weight) in pregnant rats whereas having no effect on urinary excretion of endothelin. Homocysteine treatment had no effect on mean arterial pressure (MAP) in pregnant rats (104 +/- 2 vs. 107 +/- 3 mm Hg) nor on the chronic pressure-natriuresis relationship.


CONCLUSIONS
These results suggest that although hyperhomocysteinemia decreases nitric oxide (NO) production in pregnant rats, hyperhomocysteinemia does not affect MAP, the chronic pressure-natriuresis relationship, or urinary excretion of endothelin in pregnant rats. Moreover, the reported two- to threefold elevation in plasma level of homocysteine in women with preeclampsia is unlikely to contribute to the hypertension of preeclampsia.
Chandler
Derrick L
DL
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Llinas
Maria T
MT
Reckelhoff
Jane F
JF
LaMarca
Babbette
B
Speed
Joshua
J
Granger
Joey P
JP
D000818:Animals; D001794:Blood Pressure; D005260:Female; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism* / Q000503:physiopathology*; D051381:Rats
D006710:Homocysteine; D009569:Nitric Oxide