title: Ca2+ influx mediates enhanced alpha2-adrenergic contraction in aortas from rats treated with NOS inhibitor.
abstract: Previously, we reported that aortic segments from rats made hypertensive with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA) exhibit enhanced contractile sensitivity to both alpha2-adrenergic receptor (alpha2-AR) stimulation and to KCl-induced depolarization. We hypothesized that increased contractile responses to these agents was due to a change in the common effector L-type voltage-dependent calcium channel (VDCC). In aortic segments from control and L-NNA-treated rats, contraction to the alpha2-AR agonist UK-14304 stimulated Ca2+ influx but released intracellular Ca2+ only in control arteries. UK-14304-induced contraction was blocked by the VDCC antagonist nifedipine in both control and L-NNA aortas but contraction of aortas from L-NNA-treated rats was blocked by lower concentrations. Calcium imaging studies in fura 2-loaded freshly isolated aortic vascular smooth muscle cells also demonstrated UK-14304-stimulated Ca2+ influx sensitive to nifedipine only in cells from L-NNA-treated rats. We conclude that alpha2-AR contraction in the rat aorta is mediated primarily by Ca2+ influx and that L-NNA-induced hypertension increases the dependence of this contraction on VDCCs.
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, Health Sciences Center, University of New Mexico, Albuquerque, New Mexico 87131-5218, USA. hmukundan@salud.unm.edu
authors.forename: H
authors.initials: H
authors.lastname: Mukundan
authors.forename: N L
authors.initials: NL
authors.lastname: Kanagy
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000493:pharmacokinetics*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D019335:Nitroarginine; D000068438:Brimonidine Tartrate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019001:Nitric Oxide Synthase; D009543:Nifedipine; D002118:Calcium