Role of ATP-sensitive potassium channels in normal and hypertension-associated pregnancy in rats.
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.
Lima
R
R
Universidade Federal de São Paulo, Renal Division, São Paulo, Brazil.
Tardim
J C B M
JC
Barros
M E
ME
Boim
M A
MA
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D046110:Hypertension, Pregnancy-Induced / Q000209:etiology*; D054086:KATP Channels; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D011507:Proteinuria / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; C092520:uK-ATP-1 potassium channel; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D005905:Glyburide