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 Nω‐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.
Number of times cited: 6
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- Jeffrey L. Segar, Neurohumoral and Autonomic Regulation of Blood Pressure, Pediatric Hypertension, 10.1007/978-3-319-31107-4_1, (3-26), (2018).
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- Ihor V. Yosypiv, Vasoactive Factors and Blood Pressure in Children, Pediatric Hypertension, 10.1007/978-3-319-31420-4_2-1, (1-19), (2017).
- I. Tebot, J.-M. Bonnet, C. Paquet, J.-Y. Ayoub, S. M. Da Silva, V. Louzier and A. Cirio, The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins1, Journal of Animal Science, 90, 4, (1192), (2012).
- Jeffrey L. Segar, Neural Regulation of Blood Pressure During Fetal and Newborn Life, Fetal and Neonatal Physiology, 10.1016/B978-1-4160-3479-7.10070-9, (789-798), (2011).