RESUMEN
OBJECTIVES: To identify the mechanisms underlying hypotension during the early phase of severe acute pancreatitis (SAP) by analyzing whether an impaired response to vasoactive substances occurs in this pathological process. METHODS: Experimental SAP was induced by infusing 5% sodium taurocholate through the main pancreatic duct in rats. Once mean arterial pressure (MAP) in animals with pancreatitis was reduced, different vasoactive substances and inhibitors were administered. RESULTS: Administration of the nonspecific nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester caused a similar increase in MAP in rats with pancreatitis and control rats, whereas inducible nitric oxide synthase inhibition did not cause changes in MAP. Moreover, the hypertensive response to endothelin and angiotensin II was lower in pancreatitis. Inhibition of angiotensin II synthesis by the angiotensin-converting enzyme inhibitor perindopril in animals with pancreatitis caused severe hypotension, causing death in 40% of them. Finally, pressor hyporesponsiveness to angiotensin II in animals with pancreatitis was avoided by previous administration of perindopril and N omega-nitro-L-arginine methyl ester. CONCLUSIONS: The SAP-induced hypotension is associated with a deficient pressor responsiveness to angiotensin II and endothelin-1. The renin-angiotensin system plays an important role in the control of MAP in animals with pancreatitis.
Asunto(s)
Presión Sanguínea , Hipotensión/etiología , Pancreatitis Aguda Necrotizante/fisiopatología , Vasoconstricción , Angiotensina II/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Endotelinas/metabolismo , Inhibidores Enzimáticos/farmacología , Homeostasis , Hipotensión/metabolismo , Hipotensión/fisiopatología , Masculino , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Pancreatitis Aguda Necrotizante/inducido químicamente , Pancreatitis Aguda Necrotizante/complicaciones , Pancreatitis Aguda Necrotizante/metabolismo , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , Ácido Taurocólico , Vasoconstricción/efectos de los fármacos , VasodilataciónRESUMEN
OBJECTIVES: To investigate the effect of treatment with several vasodilatory substance on the changes in mean arterial pressure (MAP) of severe acute pancreatitis. METHODS: Pancreatitis was induced in rats by 5% sodium taurocholate retrograde infusion through the pancreatic duct, which produces a significant decrease in arterial blood pressure. RESULTS: Three hours after the induction of pancreatitis, a fall of approximately 25 mm Hg in MAP was observed, with no changes of MAP in untreated controls. The administration of the nitric oxide synthesis inhibitor, N-nitro-L-arginine methyl ester (25 mg/kg), previously to the induction of pancreatitis, produced a marked fall in MAP leading to the death of all the animals. When several vasodilatory substances, S-nitroso-N-acetylpenicillamine (200 microg x kg x h), calcitonin gene-related peptide (10 microg/kg), and vasoactive intestinal polypeptide (8 microg x kg x h) were administered previously to the induction of pancreatitis, the MAP fall induced by pancreatitis was not observed. The improvement of physiological conditions observed in vasodilator-treated animals is in agreement with histological data, which show only minor structural changes in the pancreas from these animals, in contrast with the severe alterations observed in untreated pancreatitic rats. CONCLUSION: : Vasodilation confers protection against the systemic circulatory derangement derived from the development of severe acute pancreatitis.
Asunto(s)
Pancreatitis/tratamiento farmacológico , Choque/prevención & control , Vasodilatadores/uso terapéutico , Enfermedad Aguda , Amilasas/sangre , Animales , Presión Sanguínea/efectos de los fármacos , Péptido Relacionado con Gen de Calcitonina/uso terapéutico , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/fisiología , Pancreatitis/complicaciones , Pancreatitis/patología , Pancreatitis/fisiopatología , Penicilamina/análogos & derivados , Penicilamina/uso terapéutico , Ratas , Ratas Wistar , Péptido Intestinal Vasoactivo/uso terapéutico , Vasodilatadores/farmacologíaRESUMEN
We validated the pig eye as a model of glaucoma, based on chronic elevation of intraocular pressure (IOP). IOP was elevated by cauterising three episcleral veins in each of the left eyes of five adult pigs. Right eyes were used as controls. Measurement of IOP was performed during the experiment with an applanation tonometer (Tono-Pen). Five months after episcleral vein occlusion, retinal ganglion cells (RGCs) from both cauterised and control eyes were retrogradely backfilled with Fluoro-Gold. Analysis of RGC loss and morphometric as characterization of surviving RGCs was performed using whole-mounted retinas. Elevation of IOP was apparent after three weeks of episcleral vein cauterisation and it remained elevated for at least 21 weeks (duration of the experiments). Analysis of RGC loss after chronic elevation of IOP revealed that RGC death was significant in the mid-peripheral and peripheral retina, mainly in the temporal quadrants of both retinal regions. Moreover the mean soma area of remaining RGCs was observed to increase and we found a greater loss of large RGCs in the mid-peripheral and peripheral retina. We conclude that the pattern of RGC death induced in the pig retina by episcleral vein cauterisation resembles that found in human glaucoma. On the basis of this study, the pig retina may be considered as a suitable model for glaucoma-related studies, based on its similarity with human and on its affordability.