title: Influence of calcium-dependent potassium channel blockade and nitric oxide inhibition on norepinephrine-induced contractions in two forms of genetic hypertension.
abstract: The activation of Ca(2+)-dependent K(+) channels (BK(Ca)) leads to the attenuation of vascular contraction. Our study aimed to evaluate BK(Ca) influence on norepinephrine (NE)-induced femoral artery contraction in two forms of genetic hypertension. NE dose-response curves were studied before and after BK(Ca) blockade or after combined blockade of BK(Ca) and NO synthase (NOS) in femoral arteries with intact endothelium from normotensive Wistar (WIS), hypertensive hereditary hypertriglyceridemic (HTG), or spontaneously hypertensive rats (SHR). NE-induced contractions of femoral arteries were augmented in both hypertensive strains compared with Wistar rats, but acetylcholine-induced relaxation was impaired in HTG only. The increase of basal vascular tone of isolated arteries after BK(Ca) blockade was similar in all rat strains, but subsequent NOS inhibition increased basal vascular tone more in vessels from both hypertensive rat strains. NOS inhibition increased sensitivity to NE in all strains, but BK(Ca) blockade in SHR only. Neither treatment enhanced maximal NE-induced contraction. NO-dependent attenuation of NE-induced contractions was greater in SHR than HTG or Wistar vessels, whereas large conductance Ca(2+)-dependent K(+) channels may play a greater role in modulating vascular contraction in the severe form of hypertension.
authors.affiliation: Center of Cardiovascular Research and Institute of Physiology Academy of Sciences of the Czech Republic, Prague, Czech Republic. silvia.liskova@gmail.com
authors.forename: Silvia
authors.initials: S
authors.lastname: Lísková
authors.forename: Miriam
authors.initials: M
authors.lastname: Petrová
authors.forename: Petr
authors.initials: P
authors.lastname: Karen
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kunes
authors.forename: Josef
authors.initials: J
authors.lastname: Zicha
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D019789:Tetraethylammonium; D019001:Nitric Oxide Synthase; D009638:Norepinephrine