Low-dose nitro-L-arginine administration in baboon (Papio hamadryas) pregnancy.
1. The purpose of the present study was to examine the effect of nitric oxide (NO) inhibition on mean arterial pressure (MAP), endothelin (ET) and the renin-aldosterone system in pregnancy in the non-human primate (baboon). 2. Twenty pregnant baboons (Papio hamadryas) were examined prospectively after the administration of an oral NO inhibitor in different phases of pregnancy. Haemodynamic responses to NO inhibition, evidence of pre-eclampsia and the renin-aldosterone system were examined under anaesthesia. 3. Oral NL-nitro-L-arginine (NOLA; 5 or 10 mg/kg) was given for 1 week in early (6-8 weeks gestation), middle (14-16 weeks gestation) and late (22-24 weeks gestation) pregnancy and while non-pregnant. Mean arterial pressure, heart rate, haematology, biochemistry, ET, plasma renin activity (PRA) and aldosterone were measured. Foetal effects of NOLA were also examined by ultrasound and neonatal measurements. 4. Nitric oxide inhibition led to an increase in MAP in non-pregnant animals (9 mmHg) and in middle and later pregnancy (6 and 7 mmHg, respectively). Mean arterial pressure in early pregnancy was not affected. A reduction in PRA occurred after NO inhibition in all stages of pregnancy. Significant proteinuria occurred only in late pregnancy. 5. Nitric oxide is involved in the maintenance of lower blood pressure in late pregnancy and inhibition leads to an increase in blood pressure and proteinuria in the baboon. Nitric oxide insufficiency may contribute to the clinical manifestations of human pre-eclampsia. Nitric oxide was not involved in the normal vasodilation of early primate pregnancy.
Hennessy
A
A
Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. Ahennese@renicu.rps.cs.nsw.gov.au
Gillin
A G
AG
Duggin
G G
GG
Horvath
J S
JS
Tiller
D J
DJ
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016232:Endothelins / Q000097:blood / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D010215:Papio; D011225:Pre-Eclampsia / Q000139:chemically induced; D011247:Pregnancy; D012083:Renin / Q000097:blood
D016232:Endothelins; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D000450:Aldosterone; D012083:Renin