The effect of chronic nitric oxide synthase inhibition on blood pressure and heart rate in unrestrained pregnant rats as recorded by radiotelemetry

Am J Obstet Gynecol. 1999 Jul;181(1):159-64. doi: 10.1016/s0002-9378(99)70453-9.

Abstract

Objectives: The objective of this study was to determine the effect of chronic nitric oxide synthase inhibition on heart rate and intravascular blood pressure in unrestrained pregnant rats as recorded by radiotelemetry.

Study design: Heart rate and systolic and diastolic blood pressures were monitored beginning with day 6 of pregnancy and until 1 week post partum with a radiotelemetric device. On day 10 of pregnancy osmotic minipumps were implanted subcutaneously and loaded to continuously deliver N(G)-nitro-L -arginine methyl ester (50 mg/d per rat, n = 6 animals) or vehicle (control group, n = 6 animals).

Results: Blood pressure in the animals treated with N(G)-nitro-L -arginine methyl ester significantly increased compared with that in the control group and heart rate significantly decreased immediately after nitric oxide synthase blockade. Blood pressure then trended downward as gestation progressed, until the difference between the control group and the group treated with N(G)-nitro-L -arginine methyl ester became nonsignificant after day 17. Refractoriness to nitric oxide synthase blockade was especially evident in the diastolic pressure. Systolic, diastolic, and mean blood pressures in the rats treated with N(G)-nitro-L -arginine methyl ester were again significantly higher than those in the control group immediately after delivery and remained so despite a lower heart rate until the experiment was ended on postpartum day 6.

Conclusions: Radiotelemetry can be used to monitor heart rate and intra-arterial blood pressure in unstressed, unrestrained animals. Chronic inhibition of nitric oxide does not cause sustained hypertension throughout pregnancy. Nitric oxide does not appear to be the only factor responsible for the vascular changes in pregnancy. The factors responsible for the refractoriness to nitric oxide synthase blockade are specific to pregnancy and disappear immediately after delivery.

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Female
  • Gestational Age
  • Heart Rate / drug effects*
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Pre-Eclampsia / etiology
  • Pre-Eclampsia / physiopathology*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Telemetry

Substances

  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester