nitroarginine and Vascular-Diseases

Endothelium dysfunction is believed to play a role in the development of cardiovascular disease. The aim of the present study was to evaluate the suitability of organ culture as a model for endothelium dysfunction.. The isometric tension was recorded in isolated segments of the rat mesenteric artery branch, before and after organ culture for 20 h. Vasodilatation was expressed as % of preconstriction with U46619. The acetylcholine (ACh) induced nitric oxide (NO) mediated dilatation was studied in the presence of 10 microM indomethacin, 50 nM charybdotoxin and 1 microM apamin. Endothelium-derived hyperpolarising factor (EDHF) was studied in the presence of 0.1 mM L-NOARG and indomethacin. Prostaglandins were studied in the presence of L-NOARG, charybdotoxin and apamin.. The ACh-induced NO and prostaglandin-mediated dilatations decreased significantly during organ culture (NO: 84% in control and 36% in cultured; prostaglandins: 48% in control and 16% in cultured). Notably, the total ACh-dilatation was not changed. This might be explained by the finding that EDHF alone stimulated a full dilatation even after organ culture (83% in control and 80% in cultured). EDHF may thereby compensate for the loss in NO and prostaglandin-mediated dilatation. Dilatations induced by forskolin or sodium nitroprusside did not change after organ culture, indicating intact smooth muscle cell function.. Organ culture induces a loss in NO and prostaglandin-mediated dilatation, which is compensated for by EDHF. This shift in mediator profile resembles that in endothelium dysfunction. Organ culture provides an easily accessible model where the molecular changes that take place, when endothelium dysfunction is developed, can be examined over time.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Animals; Apamin; Biological Factors; Charybdotoxin; Endothelium, Vascular; Enzyme Inhibitors; Female; Indomethacin; Mesenteric Arteries; Nitric Oxide; Nitroarginine; Organ Culture Techniques; Rats; Rats, Sprague-Dawley; Time Factors; Vascular Diseases; Vasoconstrictor Agents; Vasodilation

Inhibition of an endothelium-derived relaxing factor (EDRF) may contribute to the pathogenesis of thrombotic arterial occlusions.. We measured the blood pressure and urinary excretion of protein, sodium, and potassium and histologically examined the brains, hearts, and kidneys in normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) fed on a diet containing: (a) EDRF inhibitor (L-N-nitroarginine:L-NNA); (b) L-arginine, which reverses the effect of L-NNA; or (c) both L-NNA and L-arginine for 1 to 8 weeks. In addition, we examined L-NNA-treated SHRSP, the blood pressures of which were lowered using hydralazine. Furthermore, we produced and examined Goldblatt's renal hypertensive rats, which are of a different type from those resulting from the L-NNA treatment.. Both WKY and SHRSP rats fed on a diet containing L-NNA suffered from hypertension and cerebral infarctions in a dose-dependent manner. Cerebral infarctions occurred whether or not SHRSP rats were treated with an antihypertensive agent when they were fed a high dosage of L-NNA. In contrast, SHRSP rats, treated simultaneously with both L-NNA and L-arginine, suffered few cerebral infarctions, although they were severely hypertensive. In addition, there were no cerebral infarctions in Goldblatt's renal hypertensive rats, although they suffered from advanced hypertension.. The data indicate that the inhibition of EDRF injures the vessel walls and encourages platelet adhesion to the damaged areas. The adhering platelets narrow the lumen with resultant thrombotic arterial occlusions. Pathophysiologic conditions that decrease EDRF synthesis appear to play an important role in cerebral, renal, and myocardial infarctions.

Topics: Animals; Arginine; Arterial Occlusive Diseases; Blood Pressure; Blood Vessels; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Hydralazine; Hypertension, Renovascular; Incidence; Microscopy, Electron; Nitric Oxide; Nitroarginine; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium; Thrombosis; Time Factors; Vascular Diseases