< Terug naar vorige pagina

Publicatie

Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries

Tijdschriftbijdrage - Tijdschriftartikel

Arterial hypertension (AHT) affects the voltage dependency of L-type Ca2+ channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)-induced AHT on L-type Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ channel-mediated contraction of conduit arteries. This effect may contribute to the decreased vascular compliance in AHT and explain the efficacy of Ca2+ channel blockers to reduce vascular stiffness and central blood pressure in AHT.
Tijdschrift: Pflügers Archiv
ISSN: 0031-6768
Volume: 468
Pagina's: 257 - 267
Jaar van publicatie:2016
Trefwoorden:A1 Journal article
BOF-keylabel:ja
BOF-publication weight:2
CSS-citation score:1
Authors from:Higher Education
Toegankelijkheid:Open