title: The effect of ischaemia on endothelium-dependent vasodilatation and adrenoceptor-mediated vasoconstriction in rat isolated hearts.
abstract: 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 alpha-adrenoceptor agonists in the rat coronary vasculature. 2. In rat isolated, Langendorff perfused hearts, inhibition of NO with haemoglobin (Hb, 6 microM) 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 alpha-adrenoceptor agonist, noradrenaline (NA, 0.1-10 nmol) and the alpha 2-adrenoceptor agonist, B-HT 920 (0.001-1 mumol) but had no effect on the vascular response to the alpha 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 alpha 2-adrenoceptors. Ischaemia and reperfusion in this isolated vascular bed caused only a small increase in the coronary vasoconstrictor response to alpha 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 alpha-adrenoceptor-mediated constriction.
authors.affiliation: Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Pannangpetch
authors.forename: O L
authors.initials: OL
authors.lastname: Woodman
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000503:physiopathology; D006454:Hemoglobins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D006454:Hemoglobins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D009638:Norepinephrine