Universidade Federal de Minas Gerais

About: Universidade Federal de Minas Gerais is a education organization based out in Belo Horizonte, Minas Gerais, Brazil. It is known for research contribution in the topics: Population & Immune system. The organization has 41631 authors who have published 75688 publications receiving 1249905 citations.

Evidence for a Functional Interaction of the Angiotensin-(1–7) Receptor Mas With AT1 and AT2 Receptors in the Mouse Heart

Abstract: The aim of this study was to evaluate the angiotensin (Ang)-(1-7) effects in isolated mouse hearts. The hearts of male C57BL/6J and knockout mice for the Ang-(1-7) receptor Mas were perfused by the Langendorff method. After a basal period, the hearts were perfused for 20 minutes with Krebs-Ringer solution (KRS) alone (control) or KRS containing Ang-(1-7) (0.22 pmol/L), the Mas antagonist A-779 (115 nmol/L), the angiotensin type 1 receptor antagonist losartan (2.2 micromol/L), or the angiotensin type 2 receptor antagonist PD123319 (130 nmol/L). To evaluate the involvement of Ang receptors, prostaglandins, and nitric oxide in the Ang-(1-7) effects, the hearts were perfused for 20 to 30 minutes with KRS containing either A-779, losartan, PD123319, indomethacin, or NG-nitro-L-arginine methyl ester (L-NAME) alone or in association with subsequent Ang-(1-7) perfusion. In addition, hearts from Mas-knockout mice were perfused for 20 minutes with KRS containing Ang-(1-7) (0.22 pmol/L) and losartan. Ang-(1-7) alone did not change the perfusion pressure. Strikingly, in the presence of losartan, 0.22 pmol/L Ang-(1-7) induced a significant decrease in perfusion pressure, which was blocked by A-779, indomethacin, and L-NAME. Furthermore, this effect was not observed in Mas-knockout mice. In contrast, in the presence of PD123319, Ang-(1-7) produced a significant increase in perfusion pressure. This change was not modified by the addition of A-779. Losartan reduced but did not abolish this effect. Our results suggest that Ang-(1-7) produces complex vascular effects in isolated, perfused mouse hearts involving interaction of its receptor with angiotensin type 1- and type 2-related mechanisms, leading to the release of prostaglandins and nitric oxide.

The peripheral antinociceptive effect induced by morphine is associated with ATP-sensitive K+ channels

Abstract: The effect of several K+ channel blockers such as glibenclamide, tolbutamide, charybdotoxin (ChTX), apamin, tetraethylammonium (TEA), 4-aminopyridine (4-AP) and cesium on the peripheral antinociceptive effect of morphine was evaluated by the paw pressure test in Wistar rats. The intraplantar administration of a carrageenan suspension (250 μg) resulted in an acute inflammatory response and a decreased threshold to noxious pressure. Morphine administered locally into the paw (25, 50, 100 and 200 μg) elicited a dose-dependent antinociceptive effect which was demonstrated to be mediated by a peripheral site up to the 100 μg dose. The selective blockers of ATP-sensitive K+ channels glibenclamide (20, 40 and 80 μg paw−1) and tolbutamide (40, 80 and 160 μg paw−1) antagonized the peripheral antinociception induced by morphine (100 μg paw−1). This effect was unaffected by ChTX (0.5, 1.0 and 2.0 μg paw−1), a large conductance Ca2+-activated K+ channel blocker, or by apamin (2.5, 5.0 and 10.0 μg paw−1), a selective blocker of a small conductance Ca2+-activated K+ channel. Intraplantar administration of the non-specific K+ channel blockers TEA (160, 320 and 640 μg), 4-AP (10, 50 and 100 μg) and cesium (125, 250 and 500 μg) also did not modify the peripheral antinociceptive effect of morphine. These results suggest that the peripheral antinociceptive effect of morphine may result from activation of ATP-sensitive K+ channels, which may cause a hyperpolarization of peripheral terminals of primary afferents, leading to a decrease in action potential generation. In contrast, large conductance Ca2+-activated K+ channels, small conductance Ca2+-activated K+ channels as well as voltage-dependent K+ channels appear not to be involved in this transduction pathway. British Journal of Pharmacology (2000) 129, 110–114; doi:10.1038/sj.bjp.0703038