Enalapril normalizes endothelium-derived hyperpolarizing factor-mediated relaxation in mesenteric artery of adult hypertensive rats prenatally exposed to testosterone

Amar S. More, Jay S. Mishra, Gary Hankins, Chandra Yallampalli, Kunju Sathishkumar

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Prenatal exposure to elevated testosterone levels induces adult life hypertension associated with selective impairments in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in mesenteric arteries. We tested whether the angiotensin-converting enzyme inhibitor enalapril restores EDHF function through regulating the activities of small (Kcnn3) and intermediate (Kcnn4) conductance calcium-activated potassium channels in mesenteric arteries. Pregnant Sprague- Dawley rats were injected subcutaneously with vehicle or testosterone propionate (0.5 mg/kg/day from Gestation Day 15 to 19), and their 6-mo-old adult male offspring were examined. A subset of rats in these two groups was given enalapril (40 mg/ kg/day) for 2 wk through drinking water. Blood pressures were assessed through carotid arterial catheter and endotheliumdependent mesenteric arterial EDHF relaxation, using wire myography. Ace and Kcnn3 and Kcnn4 channel expression levels were also examined. Renal and vascular Ace expression and plasma angiotensin II levels were increased in testosterone offspring. Blood pressure levels were significantly higher in testosterone offspring than in controls, and treatment with enalapril significantly attenuated blood pressure in testosterone offspring. EDHF relaxation in testosterone offspring was reduced compared to that in controls, and it was significantly restored by enalapril treatment. Kcnn4 channel expression and function were similar between control and testosterone rats, but it was not affected by enalapril treatment. Relaxation mediated by Kcnn3 was impaired in testosterone offspring, and it was normalized by enalapril treatment. Furthermore, enalapril treatment restored expression levels of Kcnn3 channels. These findings suggest that enalapril has a positive influence on endothelial function with improvement in EDHF relaxation through normalization of Kcnn3 expression and activity.

Original languageEnglish (US)
Article number155
JournalBiology of Reproduction
Volume92
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Enalapril
Mesenteric Arteries
Endothelium
Testosterone
Blood Pressure
Intermediate-Conductance Calcium-Activated Potassium Channels
Myography
Testosterone Propionate
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II
Drinking Water
Blood Vessels
Sprague Dawley Rats
Catheters
Hypertension
Kidney
Pregnancy

Keywords

  • Blood pressure
  • EDHF
  • Enalapril
  • Endothelium
  • Kcnn3 channel
  • Mesenteric arteries
  • Pregnancy
  • Testosterone

ASJC Scopus subject areas

  • Cell Biology

Cite this

Enalapril normalizes endothelium-derived hyperpolarizing factor-mediated relaxation in mesenteric artery of adult hypertensive rats prenatally exposed to testosterone. / More, Amar S.; Mishra, Jay S.; Hankins, Gary; Yallampalli, Chandra; Sathishkumar, Kunju.

In: Biology of Reproduction, Vol. 92, No. 6, 155, 01.06.2015.

Research output: Contribution to journalArticle

@article{66af1f0dbbbd46279890ebb469823d33,
title = "Enalapril normalizes endothelium-derived hyperpolarizing factor-mediated relaxation in mesenteric artery of adult hypertensive rats prenatally exposed to testosterone",
abstract = "Prenatal exposure to elevated testosterone levels induces adult life hypertension associated with selective impairments in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in mesenteric arteries. We tested whether the angiotensin-converting enzyme inhibitor enalapril restores EDHF function through regulating the activities of small (Kcnn3) and intermediate (Kcnn4) conductance calcium-activated potassium channels in mesenteric arteries. Pregnant Sprague- Dawley rats were injected subcutaneously with vehicle or testosterone propionate (0.5 mg/kg/day from Gestation Day 15 to 19), and their 6-mo-old adult male offspring were examined. A subset of rats in these two groups was given enalapril (40 mg/ kg/day) for 2 wk through drinking water. Blood pressures were assessed through carotid arterial catheter and endotheliumdependent mesenteric arterial EDHF relaxation, using wire myography. Ace and Kcnn3 and Kcnn4 channel expression levels were also examined. Renal and vascular Ace expression and plasma angiotensin II levels were increased in testosterone offspring. Blood pressure levels were significantly higher in testosterone offspring than in controls, and treatment with enalapril significantly attenuated blood pressure in testosterone offspring. EDHF relaxation in testosterone offspring was reduced compared to that in controls, and it was significantly restored by enalapril treatment. Kcnn4 channel expression and function were similar between control and testosterone rats, but it was not affected by enalapril treatment. Relaxation mediated by Kcnn3 was impaired in testosterone offspring, and it was normalized by enalapril treatment. Furthermore, enalapril treatment restored expression levels of Kcnn3 channels. These findings suggest that enalapril has a positive influence on endothelial function with improvement in EDHF relaxation through normalization of Kcnn3 expression and activity.",
keywords = "Blood pressure, EDHF, Enalapril, Endothelium, Kcnn3 channel, Mesenteric arteries, Pregnancy, Testosterone",
author = "More, {Amar S.} and Mishra, {Jay S.} and Gary Hankins and Chandra Yallampalli and Kunju Sathishkumar",
year = "2015",
month = "6",
day = "1",
doi = "10.1095/biolreprod.115.130468",
language = "English (US)",
volume = "92",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "6",

}

TY - JOUR

T1 - Enalapril normalizes endothelium-derived hyperpolarizing factor-mediated relaxation in mesenteric artery of adult hypertensive rats prenatally exposed to testosterone

AU - More, Amar S.

AU - Mishra, Jay S.

AU - Hankins, Gary

AU - Yallampalli, Chandra

AU - Sathishkumar, Kunju

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Prenatal exposure to elevated testosterone levels induces adult life hypertension associated with selective impairments in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in mesenteric arteries. We tested whether the angiotensin-converting enzyme inhibitor enalapril restores EDHF function through regulating the activities of small (Kcnn3) and intermediate (Kcnn4) conductance calcium-activated potassium channels in mesenteric arteries. Pregnant Sprague- Dawley rats were injected subcutaneously with vehicle or testosterone propionate (0.5 mg/kg/day from Gestation Day 15 to 19), and their 6-mo-old adult male offspring were examined. A subset of rats in these two groups was given enalapril (40 mg/ kg/day) for 2 wk through drinking water. Blood pressures were assessed through carotid arterial catheter and endotheliumdependent mesenteric arterial EDHF relaxation, using wire myography. Ace and Kcnn3 and Kcnn4 channel expression levels were also examined. Renal and vascular Ace expression and plasma angiotensin II levels were increased in testosterone offspring. Blood pressure levels were significantly higher in testosterone offspring than in controls, and treatment with enalapril significantly attenuated blood pressure in testosterone offspring. EDHF relaxation in testosterone offspring was reduced compared to that in controls, and it was significantly restored by enalapril treatment. Kcnn4 channel expression and function were similar between control and testosterone rats, but it was not affected by enalapril treatment. Relaxation mediated by Kcnn3 was impaired in testosterone offspring, and it was normalized by enalapril treatment. Furthermore, enalapril treatment restored expression levels of Kcnn3 channels. These findings suggest that enalapril has a positive influence on endothelial function with improvement in EDHF relaxation through normalization of Kcnn3 expression and activity.

AB - Prenatal exposure to elevated testosterone levels induces adult life hypertension associated with selective impairments in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in mesenteric arteries. We tested whether the angiotensin-converting enzyme inhibitor enalapril restores EDHF function through regulating the activities of small (Kcnn3) and intermediate (Kcnn4) conductance calcium-activated potassium channels in mesenteric arteries. Pregnant Sprague- Dawley rats were injected subcutaneously with vehicle or testosterone propionate (0.5 mg/kg/day from Gestation Day 15 to 19), and their 6-mo-old adult male offspring were examined. A subset of rats in these two groups was given enalapril (40 mg/ kg/day) for 2 wk through drinking water. Blood pressures were assessed through carotid arterial catheter and endotheliumdependent mesenteric arterial EDHF relaxation, using wire myography. Ace and Kcnn3 and Kcnn4 channel expression levels were also examined. Renal and vascular Ace expression and plasma angiotensin II levels were increased in testosterone offspring. Blood pressure levels were significantly higher in testosterone offspring than in controls, and treatment with enalapril significantly attenuated blood pressure in testosterone offspring. EDHF relaxation in testosterone offspring was reduced compared to that in controls, and it was significantly restored by enalapril treatment. Kcnn4 channel expression and function were similar between control and testosterone rats, but it was not affected by enalapril treatment. Relaxation mediated by Kcnn3 was impaired in testosterone offspring, and it was normalized by enalapril treatment. Furthermore, enalapril treatment restored expression levels of Kcnn3 channels. These findings suggest that enalapril has a positive influence on endothelial function with improvement in EDHF relaxation through normalization of Kcnn3 expression and activity.

KW - Blood pressure

KW - EDHF

KW - Enalapril

KW - Endothelium

KW - Kcnn3 channel

KW - Mesenteric arteries

KW - Pregnancy

KW - Testosterone

UR - http://www.scopus.com/inward/record.url?scp=84936934962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84936934962&partnerID=8YFLogxK

U2 - 10.1095/biolreprod.115.130468

DO - 10.1095/biolreprod.115.130468

M3 - Article

VL - 92

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 6

M1 - 155

ER -