The cardiovascular and renal effects of acute and chronic inhibition of nitric oxide production in fetal sheep.
The acute and long-term effects of blockade of nitric oxide (NO) production were studied in six chronically catheterised fetal sheep aged from 116 and 118 days; six untreated fetal sheep received injections of saline. Injection of 10 mg (kg maternal body wt)(-1) of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (NOLA) to the fetus, caused an immediate rise in fetal mean arterial pressure (MAP, P < 0.005) and a reflex fall in fetal heart rate (FHR, P < 0.001). Plasma renin concentration (PRC) fell from 8.4 +/- 3.3 to 1.5 +/- 0.3 ng ml(-1) h(-1) (P < 0.001) and was dependent on MAP (P = 0.001). Glomerular filtration rate (GFR) tended to increase, but renal blood flow (RBF) velocity decreased (P < 0.001). Thus filtration fraction (FF) increased (P < 0.025). Urine flow and sodium excretion increased (P < 0.001 for both). Fractional sodium reabsorption decreased (P < 0.05). In fetuses treated with NOLA, arterial pressure was found to affect glomerular haemodynamics and renal tubular handling of sodium. No such relationships were observed in untreated fetuses. The vascular responses to acetylcholine tended to be less (P = 0.07) and the responses to noradrenaline were enhanced in NOLA-treated fetuses. There were no changes in untreated fetuses. Fetuses were then injected twice daily with either 5 mg kg(-1) NOLA or saline for the next 2 days. On the 4th day, injection of 10 mg kg(-1) NOLA did not have any effects on MAP, FHR or renal function. However, the pressor responses to angiotensin II (Ang II) were enhanced (P < 0.005), as was the response to noradrenaline but to a lesser extent. It is concluded that endothelial production of NO maintains normal fetal blood pressure, renal vascular resistance and fetal renal function. When NO production was blocked by repeated injections of NOLA, other vasodilator pathways took over the maintenance of cardiovascular and renal vascular tone. However, alterations in both cardiovascular and renal function were still present. That is, there was increased pressor sensitivity to exogenous Ang II and unmasking of effects of arterial pressure on glomerular and tubular function.
Yu
Ze-Yan
ZY
Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney 2052, Australia.
Lumbers
Eugenie R
ER
Simonetta
Giuseppe
G
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D006340:Heart Rate, Fetal / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000196:embryology*; D007677:Kidney Function Tests; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012756:Sheep; D014563:Urodynamics / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D012083:Renin; D009638:Norepinephrine