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(Hypertension. 2001;37:301.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Angiotensin II Relaxes Microvessels Via the AT₂ Receptor and Ca²⁺-Activated K⁺ (BK_Ca) Channels

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

From the Department of Pharmacology and Toxicology (C.D., R.E.W., L.F., J.D.C., G.O.C.) and the Vascular Biology Center (L.F., H.Z., J.D.C.), Medical College of Georgia, Augusta.

Correspondence to Dr Gerald O. Carrier, Department of Pharmacology and Toxicology, Medical College of Georgia, 1120 15th St, Augusta, GA 30912-2300. E-mail gcarrier{at}mail.mcg.edu

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 (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 PD123,319, 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 BK_Ca channels, leading to membrane repolarization and vasodilation. These findings provide evidence for a novel endothelium-independent vasodilatory effect of Ang II.

Key Words: angiotensin II • receptors, angiotensin • potassium channels • patch-clamp techniques

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