In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 4 ( 2003-04), p. 912-918
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.0000063883.83470.7B
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2003
detail.hit.zdb_id:
2094210-2
