Angiotensin II relaxes microvessels via the AT2 receptor and Ca2+-activated K+ (BKCa) channels

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

Research output: Contribution to journalArticle

72 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 AT1 receptor, whereas the relative expression and functional importance of the AT2 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 AT1 receptor antagonist, but was inhibited by PD123.319. a selective antagonist of AT2 receptors. In addition, reverse transcriptase-polymerase chain reaction studies revealed high amounts of AT2 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 (BKCa) channel. Subsequent whole-cell and single-channel patch-clamp studies on single myocytes demonstrated that Ang II increases the activity of BKCa channels. As in our tissue studies, the effect of Ang II on BKCa 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 AT2 receptor with subsequent opening of BKCa 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

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

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 AT2 receptor and Ca2+-activated K+ (BKCa) channels. Hypertension, 37(2 I), 301-307. https://doi.org/10.1161/01.HYP.37.2.301

Angiotensin II relaxes microvessels via the AT2 receptor and Ca2+-activated K+ (BKCa) 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 AT2 receptor and Ca2+-activated K+ (BKCa) channels', Hypertension, vol. 37, no. 2 I, pp. 301-307. https://doi.org/10.1161/01.HYP.37.2.301
Dimitropoulou C, White RE, Fuchs L, Zhang H, Catravas JD, Carrier GO. Angiotensin II relaxes microvessels via the AT2 receptor and Ca2+-activated K+ (BKCa) channels. Hypertension. 2001 Jan 1;37(2 I):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 AT2 receptor and Ca2+-activated K+ (BKCa) channels. In: Hypertension. 2001 ; Vol. 37, No. 2 I. pp. 301-307.
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