Angiotensin II relaxes microvessels via the AT 2 receptor and Ca 2+ -activated K + (BK Ca ) channels

Christiana Dimitropoulou, Richard E. White, Leslie Fuchs, Hanfang Zhang, John D. Catravas, Gerald O. Carrier

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Angiotensin II (Ang II) is one of the most potent vasoconstrictor substances, yet paradoxically. Ang II may dilate certain vascular beds via an undefined mechanism. Ang II-induced vasoconstriction is mediated by the AT 1 receptor, whereas the relative expression and functional importance of the AT 2 receptor in regulating vascular resistance and blood pressure are unknown. We now report that Ang II induces relaxation of mesenteric microvessels and that this vasodilatory response was unaffected by losartan, an AT 1 receptor antagonist, but was inhibited by PD123.319. a selective antagonist of AT 2 receptors. In addition, reverse transcriptase-polymerase chain reaction studies revealed high amounts of AT 2 receptor mRNA in smooth muscle from these same microvessels. Ang II-induced relaxation was inhibited by either tetraethylammonium or iberiotoxin, suggesting involvement of the large-conductance, calcium- and voltage-activated potassium (BK Ca ) channel. Subsequent whole-cell and single-channel patch-clamp studies on single myocytes demonstrated that Ang II increases the activity of BK Ca channels. As in our tissue studies, the effect of Ang II on BK Ca channels was inhibited by PD.123.319. but not by losartan. In light of these consistent findings from tissue physiology, molecular studies, and cellular/molecular physiology, we conclude that Ang II relaxes microvessels via stimulation of the AT 2 receptor with subsequent opening of BK Ca channels, leading to membrane repolarization and vasodilation. These findings provide evidence for a novel endothelium-independent vasodilatory effect of Ang II.

Original languageEnglish (US)
Pages (from-to)301-307
Number of pages7
JournalHypertension
Volume37
Issue number2 I
DOIs
StatePublished - Jan 1 2001

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Microvessels
Angiotensin II
Losartan
Tetraethylammonium
Vasoconstrictor Agents
Vasoconstriction
Reverse Transcriptase Polymerase Chain Reaction
Vasodilation
Vascular Resistance
Muscle Cells
Endothelium
Smooth Muscle
Blood Vessels
Potassium
Blood Pressure
Calcium
Messenger RNA

Keywords

  • Angiotensin
  • Angiotensin II
  • Patch-clamp techniques
  • Potassium channels
  • Receptors

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Dimitropoulou, C., White, R. E., Fuchs, L., Zhang, H., Catravas, J. D., & Carrier, G. O. (2001). Angiotensin II relaxes microvessels via the AT 2 receptor and Ca 2+ -activated K + (BK Ca ) channels Hypertension, 37(2 I), 301-307. https://doi.org/10.1161/01.HYP.37.2.301

Angiotensin II relaxes microvessels via the AT 2 receptor and Ca 2+ -activated K + (BK Ca ) channels . / Dimitropoulou, Christiana; White, Richard E.; Fuchs, Leslie; Zhang, Hanfang; Catravas, John D.; Carrier, Gerald O.

In: Hypertension, Vol. 37, No. 2 I, 01.01.2001, p. 301-307.

Research output: Contribution to journalArticle

Dimitropoulou, C, White, RE, Fuchs, L, Zhang, H, Catravas, JD & Carrier, GO 2001, ' Angiotensin II relaxes microvessels via the AT 2 receptor and Ca 2+ -activated K + (BK Ca ) channels ', Hypertension, vol. 37, no. 2 I, pp. 301-307. https://doi.org/10.1161/01.HYP.37.2.301
Dimitropoulou, Christiana ; White, Richard E. ; Fuchs, Leslie ; Zhang, Hanfang ; Catravas, John D. ; Carrier, Gerald O. / Angiotensin II relaxes microvessels via the AT 2 receptor and Ca 2+ -activated K + (BK Ca ) channels In: Hypertension. 2001 ; Vol. 37, No. 2 I. pp. 301-307.
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