Effects of Long-term Nitric Oxide Synthesis Inhibition on Plasma Volume Expansion and Fetal Growth in the Pregnant Rat

Hypertension ◽  
1995 ◽  
Vol 26 (6) ◽  
pp. 1019-1023 ◽  
Author(s):  
Sofía P. Salas ◽  
Fernando Altermatt ◽  
Mauricio Campos ◽  
Andrea Giacaman ◽  
Pedro Rosso
Keyword(s):  
Nitric Oxide ◽  
Fetal Growth ◽  
Plasma Volume ◽  
Volume Expansion ◽  
Nitric Oxide Synthesis ◽  
Plasma Volume Expansion ◽  
Pregnant Rat ◽  
Synthesis Inhibition

scholarly journals Effects of sildenafil on maternal hemodynamics and fetal growth in normal rat pregnancy

2010 ◽  
Vol 298 (2) ◽  
pp. R433-R438 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Chris Baylis
Keyword(s):  
Blood Pressure ◽  
Fetal Growth ◽  
Plasma Volume ◽  
Volume Expansion ◽  
Pde5 Inhibitor ◽  
Maternal Plasma ◽  
Sodium Retention ◽  
Maternal Weight ◽  
Plasma Volume Expansion ◽  
Normal Rat

It has been suggested that the phosphodiesterase-5 (PDE5) inhibitor sildenafil may be useful in the treatment of hypertension during pregnancy. However, we have reported a selective increase in renal inner medullary PDE5 that participates in the sodium retention of pregnancy. Therefore, the purpose of this study was to determine whether oral sildenafil treatment impairs maternal plasma volume expansion and/or fetal growth during rat pregnancy. Rats received sildenafil (10 mg·kg−1·day−1, 50 mg·kg−1·day−1, or 90 mg·kg−1·day−1) or vehicle on days 4–20 of pregnancy. On days 14–19, rats were housed in metabolic cages for collection of urine and measurement of food and water intake. Terminal hemodynamic and fetal measurements were taken on day 20. None of the sildenafil doses lowered blood pressure, and although all doses increased plasma cGMP concentrations, only the highest dose increased aortic and inner medullary cGMP content. Sildenafil had no effect on maternal weight gain; however, the highest dose decreased both plasma volume and renal sodium retention. The pup number and size were similar among the groups. Therefore, these studies suggest that low doses of systemic sildenafil may be safe during pregnancy in the rat, but higher doses may interfere with the physiological sodium retention and volume expansion of pregnancy. The effects of systemic sildenafil on blood pressure and sodium retention during hypertension in human pregnancy remain to be examined.

scholarly journals Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat

2010 ◽  
Vol 299 (4) ◽  
pp. F810-F814 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Xi-Ping Ni ◽  
Michael H. Humphreys ◽  
Chris Baylis
Keyword(s):  
Nitric Oxide ◽  
Volume Expansion ◽  
Collecting Duct ◽  
Pde5 Inhibitor ◽  
Nitric Oxide Donor ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Fractional Excretion Of Sodium ◽  
Phosphodiesterase 5

Pregnancy is characterized by plasma volume expansion and renal sodium retention with loss of natriuretic response to atrial natriuretic peptide due to increased medullary phosphodiesterase-5 (PDE5). Here, we determined whether natriuretic responses to nitric oxide (NO) are also blunted in pregnancy due to increased PDE5. Anesthetized 16-day pregnant and virgin rats were studied at baseline and during intrarenal infusion of the NO donor spermine NONOate (2.5 nmol/min), the PDE5 inhibitor sildenafil (SILD; 0.5 μg/min), or a combination. The right (noninfused) kidney served as a control. Intrarenal NONOate had no effect on mean arterial pressure (MAP); however, SILD reduced MAP in virgin rats, and the combination of NONOate+SILD reduced MAP in both virgin and pregnant rats. Neither NONOate nor SILD altered glomerular filtration rate. NONOate and SILD each stimulated sodium excretion (UNaV) and fractional excretion of sodium (FENa) in virgin rats, but the combination did not result in an additional natriuretic response. However, NONOate infusion did not increase UNaV or FENa in pregnant rats, but the natriuretic response to NONOate was restored with SILD, and SILD alone produced a natriuresis during pregnancy. Sodium nitroprusside (10−4 mol/l)-stimulated cGMP accumulation from inner medullary collecting duct cells was blunted in cells from pregnant vs. virgin or postpartum rats and was restored by treatment with the PDE5 inhibitor DMPPO (10−7 mol/l). Therefore, increased intrarenal PDE5 mediates the blunted natriuretic response to NO, and loss of responsiveness to the cGMP-dependent, natriuretic agents may contribute to volume expansion during pregnancy.

Effect of acute plasma volume expansion on peripheral arteriolar tone in healthy subjects

1992 ◽  
Vol 83 (5) ◽  
pp. 541-547 ◽  
Author(s):  
Alison Calver ◽  
Joe Collier ◽  
Daniel Green ◽  
Patrick Vallance
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Plasma Volume ◽  
Healthy Subjects ◽  
Volume Expansion ◽  
Forearm Blood Flow ◽  
Plasma Volume Expansion ◽  
Arterial Infusion ◽  
Vasodilator Response ◽  
Flow Response

1. Using venous occlusion plethysmography, we have investigated the forearm blood flow response in healthy subjects to the acute plasma volume expansion caused by a rapid intravenous infusion of saline. The contribution made to this response by nitric oxide has been investigated using local intra-arterial infusions of the nitric oxide synthase inhibitor NG-monomethyl-l-arginine. 2. The infusion of 1000 ml of saline over 25 min caused plasma volume to increase by about 7%, and resulted in a rise in forearm blood flow, with no change in arterial blood pressure. The onset of the blood flow response occurred within 10 min and blood flow remained elevated above baseline 20 mm after the end of the saline infusion. 3. Local intra-arterial infusion of NG-monomethyl-l-arginine alone caused a reduction in forearm blood flow which was maximal at the end of the infusion and gradually recovered to baseline levels over 40 min. 4. When local intra-arterial infusion of NG-monomethyl-l-arginine was followed by plasma volume expansion, the calculated effect of NG-monomethyl-l-arginine was such as to abolish the vasodilator response to saline. 5. The effect of local intra-arterial infusion of NG-monomethyl-l-arginine on forearm blood flow was greater when the drug was given after volume expansion had occurred, than when it was given before the administration of saline. However, in control experiments the vasoconstrictor response to noradrenaline was also enhanced after the administration of the volume load in comparison with the response to noradrenaline given alone. 6. These results are consistent with the possibility that increased local synthesis of nitric oxide contributes to the vasodilator response to volume expansion.

scholarly journals Long-term infant outcome of a randomized trial of plasma volume expansion in women with preeclampsia remote from term

2004 ◽  
Vol 191 (6) ◽  
pp. S36 ◽  
Author(s):  
Wessel Ganzevoort ◽  
Annelies Rep ◽  
Aleid G. van Wassenaer ◽  
Agaath G. Kaspers ◽  
Hanneke de Vries ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Plasma Volume ◽  
Volume Expansion ◽  
Term Infant ◽  
Plasma Volume Expansion ◽  
Infant Outcome
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