nitroarginine and 1-3-dipropyl-8-cyclopentylxanthine

Adenosine (0.1-300 microM) induced concentration- and endothelium-dependent relaxation of rat renal artery (RRA). N(G)-Nitro-L-arginine (L-NOARG, 10 microM) significantly reduced adenosine-elicited dilatation, but not the application of indomethacin (10 microM), ouabain (100 microM) or tetraethylammonium (TEA, 500 microM). In the presence of high concentration of K(+) (100 mM) or glibenclamide (1 microM), adenosine-evoked relaxation was almost abolished. 8-(3-Chlorostyril)caffeine (CSC, 0.3-3 microM), a selective A(2A)-antagonist, significantly reduced adenosine-evoked dilatation in a concentration-dependent manner (pA(2)=7.29). Conversely, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nM), an A(1)-antagonist, did not alter adenosine-induced relaxation. These results indicate that adenosine produces endothelium-dependent relaxation of isolated RRA. Dilatation evoked by adenosine is mediated by predominant releasing of endothelium-derived hiperpolarizing factor (EDHF) and also in one part of nitric oxide (NO) from endothelial cells. The obtained results also suggest that RRA response to adenosine is most likely initiated by activation of endothelial adenosine A(2A) receptors.

Topics: Adenosine; Animals; Caffeine; Endothelium, Vascular; Enzyme Inhibitors; Glyburide; Indomethacin; Isotonic Solutions; Male; Models, Animal; Muscle Relaxation; Nitroarginine; Potassium Chloride; Purinergic P1 Receptor Antagonists; Rats; Rats, Wistar; Receptors, Purinergic P1; Renal Artery; Tetraethylammonium; Vasodilator Agents; Xanthines

After ischaemic preconditioning (IP), obtained by short episodes of ischaemia, cardiac protection occurs due to a reduction in myocardial metabolism through the activation of A1 adenosine receptors. The antiarrhythmic effect of IP is attributed to an increase in the release of nitric oxide (NO) by the endothelium. On the basis of the above consideration the present investigation studies the changes induced by preconditioning in coronary reactive hyperaemia (RH) and how blockade of A1 receptors and inhibition of NO synthesis can modify these changes.. In anaesthetised goats, an electromagnetic flow-probe was placed around the left circumflex coronary artery. Preconditioning was obtained with two episodes of 2.5 min of coronary occlusion, separated by 5 min of reperfusion. RH was obtained with a 15 s occlusion. In a control group (n = 7) RH was studied before and after IP. In a second group (n = 7), 0.2 mg kg-1 of 8-cyclopentyl-dipropylxanthine, an A1 receptor blocker, and in a third group (n = 7) 10 mg kg-1 of NG-nitro-L-arginine (LNNA), an NO inhibitor, were given before IP. Reactive hyperaemia was again obtained before and after IP.. In the control group, after IP, the time to peak hyperaemic flow and total hyperaemic flow decreased by about 50% and 25%, respectively. The A1 receptor blockade alone did not change RH. During A1 blockade, IP reduced the time to peak of RH similar as in control (45%), but did not alter total hyperaemic flow. LNNA alone reduced resting flow and total hyperaemic flow. After NO inhibition, IP only reduced total hyperaemic flow by about 15%, but the time to peak flow was not affected.. IP alters RH by decreasing total hyperaemic flow and reducing the time to peak hyperaemic flow. While the former effect is attributed to a reduction in myocardial metabolism through the activation of the A1 receptors, the latter is likely to be due to an increased endothelial release of NO, suggesting that in addition to a protective effect on the myocardium, IP also exerts a direct effect on the responsiveness of the coronary vasculature (vascular preconditioning).

Topics: Adenosine; Analysis of Variance; Animals; Coronary Circulation; Endothelium, Vascular; Goats; Hyperemia; Ischemic Preconditioning, Myocardial; Myocardial Ischemia; Myocardium; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Purinergic P1 Receptor Antagonists; Regional Blood Flow; Xanthines

The aim of this study was to investigate whether cardiodepressant mediators are released after myocardial ischaemia during reperfusion.. Using a double heart model, the effect of the reoxygenated coronary effluent of an isolated guinea pig heart on a sequentially perfused second heart was studied under control conditions and after 10 min ischaemia of the first heart. Investigation of the modulating role of known autacoids took place by using free radical scavengers, an NO synthase inhibitor and adenosine receptor antagonists. In order to identify the chemical nature of cardiac metabolites, the coronary effluent was also subjected to different chemical treatment modes.. No haemodynamic changes were observed during sequential perfusion under control conditions. After 10 min of global ischaemia in heart I, a marked decrease in LVP (-22%), LVdP/dtmax (-43%), LVdP/dtmin (-41%) and coronary perfusion pressure (-25%) was measured in heart II during sequential perfusion. The negative inotropic effect was rapid in onset and reversible within 5 min; free radicals, nitric oxide and adenosine were not involved. Storage of the coronary effluent of the first heart up to 24 h, heating, or protease treatment did not modify its cardiodepressant effects on the second sequentially perfused heart.. These results suggest the release--from an isolated heart after ischaemia during reperfusion--of a cardiodepressant mediator which induces a potent reversible negative inotropic effect on a sequentially perfused heart. The mediator is stable and in all probability not a protein.

Topics: Adenosine Deaminase; Adrenergic beta-Antagonists; Animals; Autacoids; Catalase; Depression, Chemical; Female; Free Radical Scavengers; Guinea Pigs; Male; Metoprolol; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Naphthalenes; Nitric Oxide Synthase; Nitroarginine; Perfusion; Phospholipases A; Purinergic P1 Receptor Antagonists; Purinergic P2 Receptor Antagonists; Pyrones; Superoxide Dismutase; Theobromine; Xanthines