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Effects of nisoldipine upon endothelial dysfunction following ischaemic and peroxidative injury in the perfused rat heart.

Abstract：

OBJECTIVE:Previous studies showed that treatment of hearts with nisoldipine improves recovery of cardiac function following ischaemia, improves reperfusion, and reduces the constrictor sensitivity to endothelin. The aim of the present study was to assess the reduction in vasodilator responses that occurs following ischaemia and reperfusion or after oxidative stress, and to determine whether nisoldipine treatment improves these dilator responses. METHODS:Isolated perfused rat hearts were studied. Coronary vessels were constricted by the addition of U46619 and dilator responses were determined with the addition of acetylcholine (endothelium dependent) or glyceryl trinitrate (endothelium independent). Responses were compared before and after low flow ischaemia (20%, 30 min) and reperfusion (30 min), or treatment with tert-butyl hydroperoxide (tBHP) (0.9 mM, 12 min, 30 min wash). RESULTS:The addition of U46619 caused a prolonged increase in perfusion pressure of 50 to 70 mm Hg which was not significantly different before and after treatment. Dilatation responses to acetylcholine were significantly reduced following ischaemia and reperfusion (34% of preischaemic values) or tBHP (47.6% of pre-tBHP values), while responses to glyceryl trinitrate were not significantly changed. In contrast, when hearts were perfused with nisoldipine, the responses to acetylcholine were significantly improved (88% of preischaemic values with 5 nM nisoldipine, and 68% to 78% of pre-tBHP values with 0.5 nM to 5 nM nisoldipine). Responses to acetylcholine following tBHP were not significantly improved when hearts were perfused with verapamil (5 nM 43.5%, 5 microM 32%, of pre-tBHP values), or diltiazem (5 nM 37%, 5 microM 31%, of pre-tBHP values). CONCLUSIONS:Ischaemia and reperfusion or oxidative stress reduced endothelium dependent responses, but not endothelium independent responses. Nisoldipine reduced the injury to endothelial cell function associated with ischaemia and reperfusion or oxidative stress.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Yaghi MM,Watts JA

doi

10.1093/cvr/27.6.990

subject

Has Abstract

pub_date

1993-06-01 00:00:00

pages

990-6

issue

eissn

0008-6363

issn

1755-3245

journal_volume

pub_type

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Effects of nisoldipine upon endothelial dysfunction following ischaemic and peroxidative injury in the perfused rat heart.