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(Stroke. 2005;36:2691.)
© 2005 American Heart Association, Inc.

Original Contributions

Constrictor and Dilator Effects of Angiotensin II on Cerebral Arterioles

Jean-Martin Vincent, MSc; Yiu Wa Kwan, BSc, PhD; Siu Lung Chan, BSc, PhD; Caroline Perrin-Sarrado, D Pharm, PhD; Jeffrey Atkinson, BA, MA, PhD Jean-Marc Chillon, D Pharm, PhD^*

From the Laboratoire de Pharmacologie (J.-M.V, S.L.C., C.P.-S., J.A., J.-M.C.), Faculté de Pharmacie de l’Université Henri Poincaré-Nancy I, 5 rue Albert Lebrun, 54000 Nancy, France; and the Department of Pharmacology (Y.W.K.), Faculty of Medicine, The Chinese University of Hong Kong, Shatin NT, Hong Kong.

Correspondence to Jeffrey Atkinson, Laboratoire de Pharmacologie, Faculté de Pharmacie, l’Université Henri Poincaré-Nancy I, 5 rue Albert Lebrun, 54000 Nancy, France. E-mail Jeffrey.Atkinson{at}pharma.uhp-nancy.fr

Background and Purpose— In light of the equivocal data on the cerebral vasoconstrictor and vasodilator actions of angiotensin II (Ang II) and the potential clinical importance of this, we investigated the effects of Ang II on rat pial arterioles.

Methods— We determined the effect of Ang I (3.10^–6 mol/L) in the absence and presence of the converting enzyme inhibitor, captopril (10^–5 mol/L) in cerebral arterioles of male Wistar rats (open-skull preparation), and those of Ang II (3.10^–12 to 3.10^–6 mol/L) in the absence and presence of the Ang II receptor (AT₁) antagonist, telmisartan (10^–5 mol/L) or the AT₂ antagonist, PD123319 (10^–5 mol/L). We examined the effect of PD123319 (10^–5 mol/L) and the Ca²⁺-activated K⁺ (BK_Ca) channel blocker, tetraethylammonium (10^–4 mol/L) on the Ang II responses in the presence of telmisartan (10^–5 mol/L).

Results— Ang II-induced dose-dependent constriction with a maximum decrease of –20.1±1.0% at 10^–6 mol/L. Captopril significantly decreased Ang I-induced vasoconstriction (–4.0±0.9 versus –21.3±2.5%; n=4). Telmisartan reversed Ang II-induced vasoconstriction (9.5±2.5 versus –20.1±1% at 10^–6 mol/L; n=5). PD123319 significantly increased Ang II-induced vasoconstriction (–12.9±0.8 versus –10.2±0.4% at 10^–6 mol/L; n=5). PD123319 abolished (–2.6±0.7 versus 9.3±1.1% at 10^–6 mol/L; n=5) whereas tetraethylammonium reversed (–12.1±1.6 versus 9.9±1.0% at 10^–6 mol/L; n=4) Ang II-induced vasodilatation in the presence of telmisartan.

Conclusion— Angiotensin is converted locally into Ang II; the overall effect of Ang II is vasoconstrictor following stimulation of the AT₁ receptor, but a vasodilator response can be evoked following stimulation of the AT₂ receptor and activation of BK_Ca.

Key Words: angiotensin AT₁ receptor • angiotensin AT₂ receptor • potassium channels, calcium-activated • rat

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