Pharmacologic opening of Ca2+-activated K+ channels modulates the impact of angiotensin II on afferent arteriolar diameter

Pamela K Carmines, J. P. Bast, R. W. Fallet, H. Ikenaga, N. Ishii

Research output: Contribution to journalArticle

Abstract

Although preglomerular vascular smooth muscle cells are endowed with Ca2+-activated K+ channels (KCa channels), little is known about the capacity of these channels to influence renal arteriolar resistance and responsive ness to depolarizing agonists. Therefore, experiments were performed to evaluate the hypothesis that opening of KCa channels can promote afferent arteriolar vasodilation and attenuate vasoconstrictor responses to angio tensin II (AngII). The effects of the synthetic KCa channel opener, NS1619, on afferent arteriolar function were assessed videometrically using the in vitro biood-perfused juxtamedullary nephron technique. NS1619 (10-300 μM) evoked concentration-dependent increases in afferent arteriolar lumen diameter which were almost entirely absent when the kidney donor had been pre-treated with the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat (2 mg). In 6 untreated kidneys, 300 μM NS1619 increased afferent diameter by 30 ± 4%, while this same concentration of the KCa channel opener did not significantly alter arteriolar diameter (108 ± 5% of baseline) in 6 enalaprilat-treated kidneys. In a second group of enalaprilat-treated kidneys, exogenous AngII (1 and 10 nM) elicited concentration-dependent reductions in afferent arteriolar diameter which were blunted by 30 μM NS1619. Accordingly, 10 nM AngII decreased afferent diameter by 39 ± 7% before and 22 ± 5% during exposure to the KCa channel opener (p<0.05). In summary, NS1619 was capable of dilating afferent arterioles, but this effect was not evident during ACE inhibition (which reduces endogenous AngII formation). Moreover, this agent suppressed arteriolar vasoconstrictor responsiveness to exogenous AngII. These observations support the contention that opening of KCa channels can influence afferent arteriolar function by modulating the vasoconstrictor influence of AngII.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

Fingerprint

Calcium-Activated Potassium Channels
angiotensin II
potassium channels
Angiotensin II
Enalaprilat
vasoconstrictor agents
kidneys
calcium
Vasoconstrictor Agents
Kidney
Enzyme inhibition
nephrons
enzyme inhibition
vasodilation
peptidyl-dipeptidase A
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme Inhibitors
blood vessels
smooth muscle
myocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Pharmacologic opening of Ca2+-activated K+ channels modulates the impact of angiotensin II on afferent arteriolar diameter. / Carmines, Pamela K; Bast, J. P.; Fallet, R. W.; Ikenaga, H.; Ishii, N.

In: FASEB Journal, Vol. 11, No. 3, 01.12.1997.

Research output: Contribution to journalArticle

@article{28c2a0a3e1b8429984f8309648313c41,
title = "Pharmacologic opening of Ca2+-activated K+ channels modulates the impact of angiotensin II on afferent arteriolar diameter",
abstract = "Although preglomerular vascular smooth muscle cells are endowed with Ca2+-activated K+ channels (KCa channels), little is known about the capacity of these channels to influence renal arteriolar resistance and responsive ness to depolarizing agonists. Therefore, experiments were performed to evaluate the hypothesis that opening of KCa channels can promote afferent arteriolar vasodilation and attenuate vasoconstrictor responses to angio tensin II (AngII). The effects of the synthetic KCa channel opener, NS1619, on afferent arteriolar function were assessed videometrically using the in vitro biood-perfused juxtamedullary nephron technique. NS1619 (10-300 μM) evoked concentration-dependent increases in afferent arteriolar lumen diameter which were almost entirely absent when the kidney donor had been pre-treated with the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat (2 mg). In 6 untreated kidneys, 300 μM NS1619 increased afferent diameter by 30 ± 4{\%}, while this same concentration of the KCa channel opener did not significantly alter arteriolar diameter (108 ± 5{\%} of baseline) in 6 enalaprilat-treated kidneys. In a second group of enalaprilat-treated kidneys, exogenous AngII (1 and 10 nM) elicited concentration-dependent reductions in afferent arteriolar diameter which were blunted by 30 μM NS1619. Accordingly, 10 nM AngII decreased afferent diameter by 39 ± 7{\%} before and 22 ± 5{\%} during exposure to the KCa channel opener (p<0.05). In summary, NS1619 was capable of dilating afferent arterioles, but this effect was not evident during ACE inhibition (which reduces endogenous AngII formation). Moreover, this agent suppressed arteriolar vasoconstrictor responsiveness to exogenous AngII. These observations support the contention that opening of KCa channels can influence afferent arteriolar function by modulating the vasoconstrictor influence of AngII.",
author = "Carmines, {Pamela K} and Bast, {J. P.} and Fallet, {R. W.} and H. Ikenaga and N. Ishii",
year = "1997",
month = "12",
day = "1",
language = "English (US)",
volume = "11",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - Pharmacologic opening of Ca2+-activated K+ channels modulates the impact of angiotensin II on afferent arteriolar diameter

AU - Carmines, Pamela K

AU - Bast, J. P.

AU - Fallet, R. W.

AU - Ikenaga, H.

AU - Ishii, N.

PY - 1997/12/1

Y1 - 1997/12/1

N2 - Although preglomerular vascular smooth muscle cells are endowed with Ca2+-activated K+ channels (KCa channels), little is known about the capacity of these channels to influence renal arteriolar resistance and responsive ness to depolarizing agonists. Therefore, experiments were performed to evaluate the hypothesis that opening of KCa channels can promote afferent arteriolar vasodilation and attenuate vasoconstrictor responses to angio tensin II (AngII). The effects of the synthetic KCa channel opener, NS1619, on afferent arteriolar function were assessed videometrically using the in vitro biood-perfused juxtamedullary nephron technique. NS1619 (10-300 μM) evoked concentration-dependent increases in afferent arteriolar lumen diameter which were almost entirely absent when the kidney donor had been pre-treated with the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat (2 mg). In 6 untreated kidneys, 300 μM NS1619 increased afferent diameter by 30 ± 4%, while this same concentration of the KCa channel opener did not significantly alter arteriolar diameter (108 ± 5% of baseline) in 6 enalaprilat-treated kidneys. In a second group of enalaprilat-treated kidneys, exogenous AngII (1 and 10 nM) elicited concentration-dependent reductions in afferent arteriolar diameter which were blunted by 30 μM NS1619. Accordingly, 10 nM AngII decreased afferent diameter by 39 ± 7% before and 22 ± 5% during exposure to the KCa channel opener (p<0.05). In summary, NS1619 was capable of dilating afferent arterioles, but this effect was not evident during ACE inhibition (which reduces endogenous AngII formation). Moreover, this agent suppressed arteriolar vasoconstrictor responsiveness to exogenous AngII. These observations support the contention that opening of KCa channels can influence afferent arteriolar function by modulating the vasoconstrictor influence of AngII.

AB - Although preglomerular vascular smooth muscle cells are endowed with Ca2+-activated K+ channels (KCa channels), little is known about the capacity of these channels to influence renal arteriolar resistance and responsive ness to depolarizing agonists. Therefore, experiments were performed to evaluate the hypothesis that opening of KCa channels can promote afferent arteriolar vasodilation and attenuate vasoconstrictor responses to angio tensin II (AngII). The effects of the synthetic KCa channel opener, NS1619, on afferent arteriolar function were assessed videometrically using the in vitro biood-perfused juxtamedullary nephron technique. NS1619 (10-300 μM) evoked concentration-dependent increases in afferent arteriolar lumen diameter which were almost entirely absent when the kidney donor had been pre-treated with the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat (2 mg). In 6 untreated kidneys, 300 μM NS1619 increased afferent diameter by 30 ± 4%, while this same concentration of the KCa channel opener did not significantly alter arteriolar diameter (108 ± 5% of baseline) in 6 enalaprilat-treated kidneys. In a second group of enalaprilat-treated kidneys, exogenous AngII (1 and 10 nM) elicited concentration-dependent reductions in afferent arteriolar diameter which were blunted by 30 μM NS1619. Accordingly, 10 nM AngII decreased afferent diameter by 39 ± 7% before and 22 ± 5% during exposure to the KCa channel opener (p<0.05). In summary, NS1619 was capable of dilating afferent arterioles, but this effect was not evident during ACE inhibition (which reduces endogenous AngII formation). Moreover, this agent suppressed arteriolar vasoconstrictor responsiveness to exogenous AngII. These observations support the contention that opening of KCa channels can influence afferent arteriolar function by modulating the vasoconstrictor influence of AngII.

UR - http://www.scopus.com/inward/record.url?scp=33750172135&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750172135&partnerID=8YFLogxK

M3 - Article

VL - 11

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -