Angiotensin II metabolic clearance rate and pressor responses in nonpregnant and pregnant women.
OBJECTIVE
Normal pregnancy is associated with reduced pressor dose-responses to infused angiotensin II. We tested the hypotheses that alterations in the metabolic clearance rate and the half-life of angiotensin II account for reduced pressor dose-responses during gestation and that angiotensin II increases circulating levels of vasodilatory prostaglandins I2 and E2 relative to thromboxane A2.


METHODS
Eleven nonpregnant and 37 pregnant (30 +/- 0.3 weeks' gestation, mean +/- SE) women were infused with angiotensin II (3.11 to 22.36 ng/min.kg) for 15 minutes, and blood was obtained to evaluate steady-state immunoreactive plasma angiotensin II and eicosanoid concentrations.


RESULTS
Angiotensin II pressor responses were dose dependent in all groups and reduced in pregnant women (p < 0.001). Basal immunoreactive plasma angiotensin II concentrations were 2.7-fold greater (p < 0.001) in pregnant versus nonpregnant women. Plasma levels reached steady state by 5 minutes of infusion, and at similar angiotensin II concentrations the increase in blood pressure was greater in nonpregnant versus pregnant women (p < 0.001). The angiotensin II metabolic clearance rate and half-life were similar in nonpregnant and pregnant women: metabolic clearance rate = 85 +/- 10 versus 68 +/- 3 ml/min.kg, respectively (p = 0.130), and half-life = 48 and 49 seconds, respectively. Plasma prostaglandin I2 (6-keto-prostaglandin F1 alpha) prostaglandin E2, and thromboxane B2 levels in pregnant women were unaffected by angiotensin II infusions.


CONCLUSIONS
Neither changes in angiotensin II metabolism nor angiotensin II-induced increases in plasma levels of prostaglandin I2, prostaglandin E2, or the prostaglandin I2/thromboxane A2 ratio appear responsible for the decreased pressor response sensitivity to infused angiotensin II observed during normal human pregnancy.
Magness
R R
RR
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
Cox
K
K
Rosenfeld
C R
CR
Gant
N F
NF
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015232:Dinoprostone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011247:Pregnancy / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012044:Regression Analysis; D013929:Thromboxane B2 / Q000097:blood
D000804:Angiotensin II; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone