title: Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries.
abstract: Arterial hypertension (AHT) affects the voltage dependency of L-type Ca(2+) channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)-induced AHT on L-type Ca(2+) channel-mediated isometric contractions in conduit arteries. AHT was induced in C57Bl6 mice with AngII-filled osmotic mini-pumps (4 weeks). Normotensive mice treated with saline-filled osmotic mini-pumps were used for comparison. Voltage-dependent contractions mediated by L-type Ca(2+) channels were studied in vaso-reactive studies in vitro in isolated aortic and femoral arteries by using extracellular K(+) concentration-response (KDR) experiments. In aortic segments, AngII-induced AHT significantly sensitized isometric contractions induced by elevated extracellular K(+) and depolarization. This sensitization was partly prevented by normalizing blood pressure with hydralazine, suggesting that it was caused by AHT rather than by direct AngII effects on aortic smooth muscle cells. The EC50 for extracellular K(+) obtained in vitro correlated significantly with the rise in arterial blood pressure induced by AngII in vivo. The AHT-induced sensitization persisted when aortic segments were exposed to levcromakalim or to inhibitors of basal nitric oxide release. Consistent with these observations, AngII-treatment also sensitized the vaso-relaxing effects of the L-type Ca(2+) channel blocker diltiazem during K(+)-induced contractions. Unlike aorta, AngII-treatment desensitized the isometric contractions to depolarization in femoral arteries pointing to vascular bed specific responses of arteries to hypertension. AHT affects the voltage-dependent L-type Ca(2+) channel-mediated contraction of conduit arteries. This effect may contribute to the decreased vascular compliance in AHT and explain the efficacy of Ca(2+) channel blockers to reduce vascular stiffness and central blood pressure in AHT.
authors.affiliation: Department of Pharmaceutical Sciences, Physiopharmacology, Campus Drie Eiken, University of Antwerp, T2, Universiteitsplein 1, 2610, Antwerp, Belgium. paul.fransen@uantwerpen.be.
authors.forename: Paul
authors.initials: P
authors.lastname: Fransen
authors.affiliation: Faculty of Medicine & Health Sciences, Pharmacology, Campus Drie Eiken, University of Antwerp, T2, Universiteitsplein 1, 2610, Antwerp, Belgium.
authors.forename: Cor E
authors.initials: CE
authors.lastname: Van Hove
authors.affiliation: Department of Pharmaceutical Sciences, Physiopharmacology, Campus Drie Eiken, University of Antwerp, T2, Universiteitsplein 1, 2610, Antwerp, Belgium.
authors.forename: Arthur J A
authors.initials: AJ
authors.lastname: Leloup
authors.affiliation: Department of Pharmaceutical Sciences, Physiopharmacology, Campus Drie Eiken, University of Antwerp, T2, Universiteitsplein 1, 2610, Antwerp, Belgium.
authors.forename: Dorien M
authors.initials: DM
authors.lastname: Schrijvers
authors.affiliation: Department of Pharmaceutical Sciences, Physiopharmacology, Campus Drie Eiken, University of Antwerp, T2, Universiteitsplein 1, 2610, Antwerp, Belgium.
authors.forename: Guido R Y
authors.initials: GR
authors.lastname: De Meyer
authors.affiliation: Department of Pharmaceutical Sciences, Physiopharmacology, Campus Drie Eiken, University of Antwerp, T2, Universiteitsplein 1, 2610, Antwerp, Belgium.
authors.forename: Gilles W
authors.initials: GW
authors.lastname: De Keulenaer
mesh_terms: D000200:Action Potentials; D000804:Angiotensin II / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D019806:Cromakalim / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D019806:Cromakalim; D000804:Angiotensin II; D009569:Nitric Oxide; D004110:Diltiazem; D011188:Potassium
keywords: Angiotensin II; Aorta; Cardiovascular system; Femoral artery; Hypertension; Isometric contraction; L-type Ca2+ channel; Vascular smooth muscle