Effects of oral contraceptive use on the renal and systemic vascular response to angiotensin II infusion

Abstract

We have previously shown that users of oral contraceptive (OC) medications exhibit increased plasma levels of angiotensin II (Ang II) with only modest hemodynamic consequences, suggesting estrogen-mediated Ang II type 1 (AT(1)) receptor downregulation. Accordingly, in 10 women who were OC users and 10 women who, as OC nonusers, served as controls, all mean age 26 +/- 1 yr, we examined the renal and peripheral hemodynamic response to graded Ang II infusion, plasma and urine cyclic guanosine monophosphate (cGMP) levels as a surrogate marker for AT(1) and/or AT(2) receptor-mediated activation of the nitric oxide pathway, and AT(1) receptor expression in skin biopsies. The OC nonusers were studied during the follicular and luteal phases of the menstrual cycle, whereas OC users were studied once during the 21-d medication phase. Subjects ingested a controlled sodium diet for 7 d before each study. Renal hemodynamic function was assessed using standard inulin and p-aminohippurate clearance techniques. AT(1) receptor mRNA levels in skin biopsy samples were assessed using a real-time PCR protocol. In response to graded Ang II infusion, OC users exhibited renal and peripheral hemodynamic responses that were augmented compared with those of OC nonusers, in conjunction with evidence of increased tissue AT(1) receptor expression. Plasma cGMP levels and 24-h urinary cGMP excretion did not differ. These data suggest that, contrary to our original hypothesis, OC use does not appear to be associated with AT(1) receptor downregulation. The factor protecting OC users from the hemodynamic impact of increased Ang II levels remains elusive.