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(Hypertension. 2002;39:474.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Intracellular Angiotensin II Stimulates Voltage-Operated Ca²⁺ Channels in Arterial Myocytes

Kimika Eto; Yusuke Ohya; Yoshito Nakamura; Isao Abe; Mitsuo Iida

From the Department of Medicine and Clinical Science, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.

Correspondence to Yusuke Ohya, MD, PhD, Department of Medicine and Clinical Science, Kyushu University, Graduate School of Medical Sciences, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. E-mail ohya{at}intmed2.med.kyushu-u.ac.jp

Although the presence of intracellular angiotensin II (Ang II) and of Ang II-binding sites has been reported, their roles in cell function have not been fully clarified. The purpose of the present study was to test the hypothesis that intracellular Ang II modifies voltage-operated Ca²⁺ channels in vascular smooth muscle. Ca²⁺ channel currents were recorded in guinea pig mesenteric arterial myocytes with the whole-cell patch-clamp method. Intracellular dialysis of Ang II increased the amplitudes of Ca²⁺ channel current (133±9% of the control with 10 nmol/L Ang II, n=16). Concomitant dialysis of the Ang II type 1 receptor antagonist, CV-11974 (1 µmol/L, n=11), but not the bath application of this drug, suppressed this Ang II action. In contrast, the dialysis of the Ang II type 2 receptor antagonist, PD123319 (1 µmol/L, n=5), failed to affect the Ang II action. Dialysis of either a phospholipase C inhibitor (U-73122, 10 µmol/L, n=5) or protein kinase C inhibitors (calphostin C, 100 nmol/L, n=5; protein kinase C inhibitor peptide-[19-36], 1 µmol/L, n=5) suppressed the Ang II action. Dialysis of KT5720 (100 nmol/L, n=5), an inhibitor of cAMP-dependent protein kinase, did not affect the Ang II action. Intracellular dialysis of angiotensin I (10 nmol/L) enhanced Ca²⁺ channel currents (13 3±8%, n=6), which were sensitive to intracellular enalaprilat (1 µmol/L, n=5) or CV-11974 (n=5). These results suggest that intracellular Ang II has a stimulating action on voltage-operated Ca²⁺ channels in vascular smooth muscle, possibly through intracellular binding sites similar to the Ang II type 1 receptor, which are associated with phospholipase C and protein kinase C.

Key Words: calcium channels • muscle, smooth, vascular • protein kinases • receptors, angiotensin II • angiotensin-converting enzyme • angiotensin

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