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(Hypertension. 2003;41:912.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Coronary Myogenic Constriction Antagonizes EDHF-Mediated Dilation

Role of K_Ca Channels

Simone Gschwend; Robert H. Henning; Dick de Zeeuw; Hendrik Buikema

From the Institute of Clinical Pharmacology, University of Groningen, Groningen, The Netherlands.

Correspondence to Simone Gschwend, Department of Clinical Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. E-mail s.gschwend{at}med.rug.nl

In hypertension, pressure-induced myogenic constriction and impaired endothelium-derived hyperpolarizing factor (EDHF)-mediated dilation may contribute to increased vasomotor tone. Myogenic constriction as well as EDHF-mediated dilation may share common signaling mechanisms, and both may control K_Ca channel activity to set arterial tone. To investigate a potential relation between the 2 mechanisms, we studied coronary arteries of Sprague-Dawley rats for individual myogenic constriction compared with EDHF-mediated dilation of the same artery. EDHF-mediated dilation was measured as the maximal dilation to acetylcholine (100 µmol/L) after preconstriction, resistant to NO inhibition (N^G-methyl-L-arginine acetate salt, L-NMMA, 100 µmol/L), and prostaglandin inhibition (indomethacin, 10 µmol/L) but abolished by charybdotoxin (100 nmol/L) plus apamin (500 nmol/L). Individual coronary myogenic constriction at an intraluminal pressure of 70 mm Hg (n=9) ranged from 6% to 44% (24±4%). EDHF-mediated dilation ranged from 18% to 84% (42±7%). Elevating pressure to 130 mm Hg (n=8) increased myogenic constriction by 2-fold (P<0.01) and decreased EDHF-mediated dilation by 2.6-fold (P<0.01). Interestingly, individual myogenic constriction inversely correlated to individual EDHF-mediated dilation (r=-0.75, P<0.001, n=17). Pretreatment with the K_Ca channel opener NS1619 (30 µmol/L) prevented coronary myogenic constriction and increased EDHF-mediated dilation by 2.2-fold (P<0.01), whereas the K_ATP channel opener cromakalim (3 µmol/L) had no effect on EDHF-mediated dilation. For comparison, in mesenteric arteries (at 70 mm Hg) low myogenic constriction (2±1%) was associated with high EDHF-mediated dilation (93±2%), and pretreatment with NS1619 had no effect. Our results demonstrate that myogenic constriction in coronary arteries antagonizes EDHF-mediated dilation. Activation of K_Ca channels with NS1619 reduces myogenic constriction and profoundly increases EDHF-mediated dilation, specifically in coronary arteries, suggesting a potential therapeutic impact to reduce coronary risk in hypertension.

Key Words: acetylcholine • autoregulation • endothelium-derived factors • constriction • potassium channels • vasodilation

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