1. Activation of vascular
ATP-sensitive K(+) (K(
ATP)) channels has been implicated in
vasodilator responses to pregnancy. 2. The effect of
glibenclamide, a K(
ATP) channel inhibitor, on systolic blood pressure (SBP) and renal function was evaluated in pregnant and non-pregnant spontaneously hypertensive rats, as well as in normotensive and hypertensive Wistar rats that had been made hypertensive by simultaneous treatment with
N(G)-nitro-l-arginine methyl ester (0.4 mg/mL) and
indomethacin (2 mg/kg, i.p.) from Day 1 of gestation. Pregnant animals received 10 mg/kg
glibenclamide for 12 days starting at Day 7. In addition, the
mRNA levels of the vascular K(
ATP) channel (Kir6.2) were estimated in aorta and kidney using real-time reverse transcription-polymerase chain reaction on Day 19 of pregnancy. 3. The decreased SBP observed in pregnant Wistar rats was paralleled by an increase in Kir6.2
mRNA levels.
Glibenclamide blunted systemic vasodilation and reduced the
mRNA expression of Kir6.2. There was no pregnancy induced vasodilation and no change in Kir6.2
mRNA expression in SHR.
Glibenclamide had no effect on pregnant SHR. Hypertensive Wistar rats exhibited high SBP, followed by increased Kir6.2
mRNA levels. The effects of
glibenclamide were not evaluated in this group because
glibenclamide induced intense
vaginal bleeding. 4. The results of the present study suggest that K(
ATP) channels may be involved in pregnancy induced vasodilation during normotensive pregnancy, but not in pregnant SHR.
Glibenclamide may have an abortive effect if administered during the early phases of gestation or in association with
nitric oxide and
prostaglandin inhibitors.