Effect of K+ATP channel inhibition on total and regional vascular resistance in guinea pig pregnancy.
Decreased vascular resistance and vasoconstrictor response during pregnancy enables an increase in cardiac output and regional blood flow to the uterine circulation. We sought to determine whether inhibition of vascular smooth muscle ATP-sensitive potassium (K+ATP) channel activity during pregnancy increased systemic and/or regional vascular resistance and resistance response to ANG II. A total of 32 catheterized, awake, pregnant or nonpregnant guinea pigs were treated with either the K+ATP channel inhibitor glibenclamide (3.5 mg/kg) or vehicle (DMSO) (n = 8/group). In nonpregnant and pregnant animals, glibenclamide raised blood pressure and systemic, uterine, and coronary vascular resistance, diminishing cardiac output and organ blood flow. Glibenclamide produced a greater rise in coronary vascular resistance in the pregnant than nonpregnant groups and increased renal and cerebral vascular resistance in the pregnant animals only. ANG II infusion raised blood pressure and systemic and renal vascular resistance and lowered cardiac output and renal blood flow in vehicle-treated animals. Glibenclamide augmented ANG II-induced systemic vasoconstriction in the nonpregnant and pregnant groups and the rise in uteroplacental vascular resistance in the pregnant animals. We concluded that K+ATP channel activity likely modulates systemic, uterine, and coronary vascular resistance and opposes ANG II-induced systemic vasoconstriction in nonpregnant and pregnant guinea pigs. Pregnancy augments K+ATP channel activity in the uterine, coronary, renal, and cerebral vascular beds and the uteroplacental circulation during ANG II infusion. Thus increased K+ATP channel activity appears to influence regional control of vascular resistance during guinea pig pregnancy but cannot account for the characteristic decrease in systemic vascular resistance and ANG II-induced systemic vasoconstrictor response.
Yale University School of Medicine, New Haven, Connecticut 06510, USA.
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Rodman
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Curran-Everett
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Morris
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Moore
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D008098:Litter Size; D010920:Placenta / Q000098:blood supply*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D014599:Uterus / Q000098:blood supply*; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000804:Angiotensin II; D005905:Glyburide