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Am J Physiol Heart Circ Physiol 275: H161-H168, 1998;
0363-6135/98 $5.00
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Vol. 275, Issue 1, H161-H168, July 1998

The endothelium modulates the contribution of chloride currents to norepinephrine-induced vascular contraction

Fred S. Lamb and Thomas J. Barna

Department of Pediatrics, University of Iowa, Iowa City, Iowa, 52242

Activation of a Cl- current is critical to agonist-induced activation of rat aortic smooth muscle contraction. Substituting extracellular Cl- with 130 mM methanesulfonate (8 mM Cl-) increases the contractile response to norepinephrine (NE) but not to KCl. We hypothesized that endothelial factors modulate this effect. Removing the endothelium (rubbing) or treatment with N-nitro L-arginine (L-NNA) markedly increased the potentiation of NE-induced contraction by low-Cl- buffer. Indomethacin had no effect. The previously demonstrated ability of Cl--channel blockers (DIDS, anthracene-9-carboxylic acid, niflumic acid) or Cl- transport inhibitors (bumetanide, bicarbonate-free buffer) to inhibit responses to NE was not altered by L-NNA. Low-Cl- buffer alone did not contract intact rings but produced nifedipine-sensitive contractile responses after rubbing or L-NNA treatment. These data suggest that the Cl- conductance of smooth muscle in intact blood vessels is low but increases with withdrawal of reduced nitric oxide (NO') or agonist stimulation. Rubbing or L-NNA increased the sensitivity of rings to KCl but not to NE. Nifedipine reduced both sensitivity and maximum response to NE in intact vessels. L-NNA increased the maximum response to NE in nifedipine-treated rings without changing sensitivity. We conclude that although NO' affects both the voltage-dependent and voltage-independent components of contraction, sensitivity to NE is determined by the voltage-dependent portion. The voltage change required for a full response to NE is dependent on activation of a Cl- current that may be under the tonic regulatory influence of NO'.

nitric oxide; N-nitro-L-arginine; nifedipine; indomethacin; methanesulfonate


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