Ca2+ influx mediates enhanced alpha(2)-adrenergic contraction in aortas from rats treated with NOS inhibitor

Previously, we reported that aortic segments from rats made hypertensive wi th the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (L-NNA) exh ibit enhanced contractile sensitivity to both alpha (2)-adrenergic receptor (alpha (2)-AR) stimulation and to KCl-induced depolarization. We hypothesi zed that increased contractile responses to these agents was due to a chang e in the common effector L-type voltage-dependent calcium channel (VDCC). I n aortic segments from control and L-NNA-treated rats, contraction to the a lpha (2)-AR agonist UK-14304 stimulated Ca2+ influx but released intracellu lar Ca2+ only in control arteries. UK-14304-induced contraction was blocked by the VDCC antagonist nifedipine in both control and L-NNA aortas but con traction of aortas from L-NNA-treated rats was blocked by lower concentrati ons. Calcium imaging studies in fura 2-loaded freshly isolated aortic vascu lar smooth muscle cells also demonstrated UK-14304-stimulated Ca2+ influx s ensitive to nifedipine only in cells from L-NNA-treated rats. We conclude t hat alpha (2)-AR contraction in the rat aorta is mediated primarily by Ca2 influx and that L-NNA-induced hypertension increases the dependence of thi s contraction on VDCCs.