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The effect of ischaemia on endothelium‐dependent vasodilatation and adrenoceptor‐mediated vasoconstriction in rat isolated hearts
Author(s) -
Pannangpetch Patchareewan,
Woodman Owen L.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16695.x
Subject(s) - vasoconstriction , vasodilation , endothelium , ischemia , vasoconstrictor agents , medicine , cardiology , anesthesia , pharmacology
1 The aim of this study was to investigate whether global ischaemia and reperfusion in rat isolated hearts affects endothelium‐dependent vasodilatation and adrenoceptor‐mediated vasoconstriction. In addition, it was first determined whether inhibition of the actions of nitric oxide (NO) influenced the responses to α‐adrenoceptor agonists in the rat coronary vasculature. 2 In rat isolated, Langendorff perfused hearts, inhibition of NO with haemoglobin (Hb, 6 μ m ) significantly inhibited the vasodilator responses to the endothelium‐dependent vasodilators, acetylcholine (ACh, 3–100 pmol), carbachol (CCh, 10–300 pmol), bradykinin (Bk, 1–30 pmol) and histamine (0.3–10 nmol) but did not affect responses to the endothelium‐independent vasodilator, sodium nitroprusside (SNP, 0.01‐1 nmol). 3 Inhibition of the action of NO by Hb significantly enhanced the vasoconstrictor response to the non‐selective α‐adrenoceptor agonist, noradrenaline (NA, 0.1–10 nmol) and the α 2 ‐adrenoceptor agonist, B‐HT 920 (0.001‐1 μmol) but had no effect on the vascular response to the α 1 ‐adrenoceptor agonist, methoxamine (MTX, 10–300 nmol). 4 In the perfused hearts ischaemia, induced by 30 min perfusion at 5% of the normal rate of flow, followed by 15 min of reperfusion (ischaemia/reperfusion) selectively impaired the vasodilator responses to ACh and CCh which act by muscarinic receptor stimulation but did not affect responses to the other endothelium‐dependent vasodilators Bk and histamine or to the endothelium‐independent dilator SNP. 5 After ischaemia/reperfusion the coronary vasoconstrictor responses to B‐HT 920 were slightly but significantly enhanced whereas the responses to NA and MTX were unaffected. 6 Thus, in the rat isolated heart, low flow induced‐ischaemia and reperfusion causes a selective impairment of muscarinic receptor‐mediated vasodilatation but does not impair responses to all endothelium‐dependent vasodilators. Enhanced constrictor responses to noradrenaline and B‐HT 920 in the presence of Hb indicates that endogenous NO modulates the constriction of coronary resistance vessels in response to stimulation of α 2 ‐adrenoceptors. Ischaemia and reperfusion in this isolated vascular bed caused only a small increase in the coronary vasoconstrictor response to α 2 ‐adrenoceptor stimulation. It appears that in the rat isolated heart the degree of endothelial dysfunction caused by ischaemia/reperfusion is insufficient to cause a functionally significant change in α‐adrenoceptormediated constriction.

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