Search

Background: Interactions among angiotensin II (Ang II), endothelin-1 (ET-1) and thromboxane A2 (TXA2) may play an important role in the regulation of renal function. The present study investigated the participation of TXA2 and ET-1 in the increase in renal vascular resistances (RVR) induced by Ang II, as well as the consequences of diabetes, hypertension, and the combination of both on this response., Methods: Isolated kidneys from male normoglycemic or streptozotocin-induced diabetic Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used. The increase in perfusion pressure (PP) produced by Ang II was studied in the absence or presence of the TXA2 receptor antagonist, ifetroban, or the ETA/ETB receptor antagonist, PD145065., Results: Systolic arterial pressure (SAP) was higher in SHR than in WKY, but diabetic rats (D) from each strain showed lower SAP values than their respective non-diabetic rats. Basal renal PP was higher in WKY and SHR than in WKY-D and SHR-D. Increases in renal PP produced by Ang II were comparable in the kidneys from all groups. Either ifetroban or PD145065 reduced the maximal Ang II response in all animals. The maximal inhibitory effect of ifetroban was higher (P<0.05) in WKY than in the other groups. However, the maximal inhibitory effect of PD145065 was lower in SHR than in the other groups., Conclusion: This study supports a role for ET-1 and TXA2 as mediators of the increase in renal vascular resistance produced by Ang II. These results indicate that the participation of ET-1 in the renal vasoconstriction produced by Ang II was reduced under hypertensive conditions, and that of TXA2 was reduced by both diabetes and hypertension.

Objectives: To examine the long-term effects of the angiotensin type I (AT1) receptor antagonist, valsartan, on fibrinolytic balance, coagulation parameters, endothelial function and structural alterations in atherosclerotic rabbits., Methods: Animals were submitted to a 1% cholesterol-enriched diet for 10 weeks. Half of the animals were treated with valsartan (3 or 10 mg/kg per day). Systolic arterial pressure was directly measured in awake rabbits. Tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor (PAI-1) activities were measured. Plasma concentrations of cholesterol, D-dimer, factor VIII and fibrinogen, as well as thrombin time, were also determined. Responses to acetylcholine, sodium nitroprusside and angiotensin II were evaluated in aortic rings. Morphometric analysis of aortic segments was also performed to calculate atherosclerotic lesion., Results: Cholesterol-fed rabbits presented systolic arterial pressure levels comparable to controls. These animals presented aortic atherosclerotic lesions. Treatment with valsartan did not alter plasma cholesterol levels or arterial pressure in any group. Acetylcholine-induced relaxations and D-dimer and t-PA activity were lower (P < 0.05) in atherosclerotic than in normal rabbits. In contrast, PAI-1 activity was higher (P < 0.05) in atherosclerotic rabbits than in controls. Valsartan increased (P < 0.05) acetylcholine-induced relaxations, D-dimer concentration and t-PA activity, and reduced intimal thickening and PAI-1 activity in cholesterol-fed rabbits. Fibrinogen concentrations and factor VIII concentrations were lower (P < 0.05) and thrombin time was higher (P < 0.05) in atherosclerotic rabbits compared to controls. Valsartan did not affect factor VIII in any group, but reduced fibrinogen levels only in hypercholesterolemic rabbits. Valsartan 10 mg/kg per day reduced (P < 0.05) thrombin time in cholesterol-fed rabbits., Conclusions: Impairment of fibrinolytic balance, associated with atherosclerosis in rabbits, appears to be related with angiotensin II via AT1receptors. The beneficial effect of valsartan on fibrinolysis seems to be related to the concomitant amelioration of endothelial dysfunction and reduction of intimal thickening, further supporting the importance of the blockade of angiotensin II actions to prevent thrombotic alterations associated with atherosclerosis.

Background: Numerous studies have shown that elevated plasma cholesterol can exacerbate renal disease. However, the effect of lipids on renal structure and vascular function in normal kidneys is less well established. Therefore, the aim of this study was to evaluate the impact of hypercholesterolaemia on glomerular structure and vascular reactivity of segmental arteries in rabbits. In addition, we also studied whether or not atorvastatin can prevent these structural and vascular alterations in hypercholesterolaemic rabbits., Methods: Male New Zealand rabbits were fed either a normal rabbit chow or a diet containing 1% cholesterol and treated or not with atorvastatin (1 mg/kg/day) for 12 weeks. Dose-response curves to acetylcholine (10(-9)-10(-4) mol/l) and sodium nitroprusside (10(-9)-10(-4) mol/l) were studied in segmental arteries in the presence or absence of the thromboxane A2/PGH2 receptor antagonist ifetroban (10(-5) mol/l). Glomerular size and structure were also evaluated., Results: Compared with control animals, hypercholesterolaemic rabbits presented glomerular hypertrophy and several types of injuries (capillary collapse, hyalinosis and alterations of Bowman's capsule), suggesting diffuse glomerulosclerosis. Segmental arteries also showed relaxing responses to acetylcholine and sodium nitroprusside which were lower than and similar to, respectively, those of control animals. The presence of ifetroban improved the acetylcholine response only in hypercholesterolaemic rabbits. Atorvastatin treatment prevented vascular and most glomerular changes associated with hypercholesterolaemia even in the presence of very high cholesterol levels., Conclusions: Atorvastatin exerts a protective effect on renal damage associated with hypercholesterolaemia even in the presence of deleterious levels of plasma cholesterol.