Acute lead-induced vasoconstriction in the vascular beds of isolated perfused rat tails is endothelium-dependent

Chronic lead exposure induces hypertension in humans and animals, affecting endothelial function. However, studies concerning acute cardiovascular effects are lacking. We investigated the effects of acute administration of a high concentration of lead acetate (100 µÌ) on the pressor response to phenylephrine (PHE) in the tail vascular bed of male Wistar rats. Animals were anesthetized with sodium pentobarbital and heparinized. The tail artery was dissected and cannulated for drug infusion and mean perfusion pressure measurements. Endothelium and vascular smooth muscle relaxation were tested with acetylcholine (5 µg/100 µL) and sodium nitroprusside (0.1 µg/100 µL), respectively, in arteries precontracted with 0.1 µM PHE. Concentration-response curves to PHE (0.001-300 µg/100 µL) were constructed before and after perfusion for 1 h with 100 µÌ lead acetate. In the presence of endothelium (E+), lead acetate increased maximal response (Emax) (control: 364.4 ± 36, Pb2+: 480.0 ± 27 mmHg; P < 0.05) and the sensitivity (pD2; control: 1.98 ± 0.07, 2.38 ± 0.14 log mM) to PHE. In the absence of endothelium (E-) lead had no effect but increased baseline perfusion pressure (E+: 79.5 ± 2.4, E-: 118 ± 2.2 mmHg; P < 0.05). To investigate the underlying mechanisms, this protocol was repeated after treatment with 100 µM L-NAME, 10 µM indomethacin and 1 µM tempol in the presence of lead. Lead actions on Emax and pD2 were abolished in the presence of indomethacin, and partially abolished with L-NAME and tempol. Results suggest that acute lead administration affects the endothelium, releasing cyclooxygenase-derived vasoconstrictors and involving reactive oxygen species.

Efeito clínico do uso do parecoxib em modelo de sinovite induzida em pôneis / Clinical effect of parecoxib in induced synovitis in horses

Um modelo experimental de sinovite em pôneis foi usado para avaliar o efeito do parecoxib, um antiinflamatório não-esteroidal (AINE) seletivo injetável. Cinco dias após indução da sinovite, três pôneis foram tratados com 0,55mg/kg/dia (IV) de parecoxib e três receberam solução salina 0,9 por cento (IV) por cinco dias. A avaliação de parâmetros clínicos dos animais e físico-químicos do líquido sinovial foi realizada antes da indução de sinovite, antes e 12, 24, 48, 72, 96 e 120 horas após o início do tratamento. A injeção intra-articular com adjuvante completo de Freund induziu sinovite de intensidade moderada a grave. Os pôneis tratados com parecoxib apresentaram diminuição do grau de claudicação; manutenção da flexão articular, do comprimento do passo, da temperatura retal e da freqüência cardíaca; e atenuação do grau de efusão articular. Embora o parecoxib, na dose utilizada, não tenha apresentado efeito sobre os parâmetros do líquido sinovial das articulações com sinovite, sua ação antipirética, antiinflamatória e principalmente analgésica foi observada.

An experimental synovitis model was used in ponies to evaluate the effect of parecoxib, a selective non steroidal anti-inflammatory drug (NSAID). Five days after synovitis induction, three ponies received parecoxib (IV) 0.55mg/kg/day and three ponies received sterile 0.9 percent saline solution (IV) for five days. Clinical parameters and synovial fluid were evaluated before synovitis induction, prior treatment and 12, 24, 48, 96, and 120 hours after the first treatment. The intra-articular injection of Freund's complete adjuvant induced a moderate to severe synovitis. The parecoxib treated ponies showed lameness reduction; maintenance of stride length, articular flexion, temperature, and heart rate; and attenuation of articular effusion. Although the used dosage of parecoxib had no effect on evaluated synovial fluid parameters, antipyretic, anti-inflammatory, and especially analgesic effects were observed.