ABSTRACT
The kidneys play an important role in blood pressure regulation under normal and pathological conditions. We examined the histological changes and expression patterns of cyclooxygenase-2, renin, and (pro)renin receptor (PRR) in the renal cortex of prehypertensive spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). Moreover, blood pressure and plasma urea, creatinine, angiotensin II, and angiotensin (1-7) levels were measured. The results showed that both strains had similar blood pressure and plasma urea and creatinine levels. The glomerular area, basement membrane thickness, collagen fiber content, and arterial wall thickness were greater in SHRs than in WKYs. By immunohistochemistry, cyclooxygenase-2 was localized in the macula densa and renal tubules of both strains. In SHRs, cyclooxygenase-2 was detected in a larger number of tubules, and the cortical expression of cyclooxygenase-2 was also increased. In both strains, PRR and renin were localized in the tubular epithelium and juxtaglomerular cells, respectively. In SHRs, PRR immunolocalization was increased in the glomerulus. The cortical expression of immature renin was markedly increased in SHRs compared to that in WKYs, while renin was significantly decreased. These changes were associated with higher plasma angiotensin II levels and lower plasma angiotensin (1-7) levels in SHRs. The results indicate that the kidneys of SHRs showed morphological changes and variations in cortical expression patterns of PRR, cyclooxygenase-2, and renin before the development of hypertension.
Subject(s)
Hypertension , Angiotensin II/metabolism , Animals , Blood Pressure , Creatinine , Cyclooxygenase 2/metabolism , Hypertension/veterinary , Kidney/pathology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Renin/metabolism , UreaABSTRACT
The convenience to count with a safe and effective pharmacological wealth for atrial fibrillation treatment had conduced, in a way, to a deep depuration of the vast array of antiarrhythmic drugs, keeping only a very restricted number of compounds with a widely proved anti-atrial activity. On the other hand, it had lead to the discovery of the pathophysiological concepts that point to novel therapeutic targets. Within these objectives is that new antiarrhythmic drugs with preferential, even selective, activity on myocardial atrium ion channels had been developed. Among these new antiarrhythmics, dofetilide, and AVE0118, are taken into account. In addition, new possibilities are opened based on the knowledge of the cardioprotective-antiarrhythmic qualities of the opioidergic system.
Subject(s)
Humans , Anti-Arrhythmia Agents , Atrial Fibrillation , Biphenyl Compounds , Phenethylamines , Potassium Channel Blockers , Sulfonamides , Administration, Oral , Anti-Arrhythmia Agents , Anti-Arrhythmia Agents/adverse effects , Anti-Arrhythmia Agents , Atrial Fibrillation , Biphenyl Compounds , Biphenyl Compounds , Electrophysiology , Heart Atria , Ion Channels , Phenethylamines , Phenethylamines , Potassium Channel Blockers , Potassium Channel Blockers , Randomized Controlled Trials as Topic , Receptors, Opioid , Sulfonamides , Sulfonamides , Time FactorsABSTRACT
Viscum album L. aqueous extract, on the Langendorff isolated and perfused heart model, decreases coronary vascular resistance, when compared to control group (36.00 +/- 2.00 vs. 15.80 +/- 1.96 dyn s cm-5). Our data support the fact that this mechanism involves NOS-2 and NOS-3 overexpression (4.65 and 7.89 times over control, respectively), which is correlated with increases in NO (6.24 +/- 2.49 vs. 147.95 +/- 2.79 pmol) and cGMP production (43.94 +/- 2.00 vs. 74.81 +/- 1.96 pmol mg-1 of tissue), compared to control values. Such an effect is antagonized by gadolinium(III) chloride, L-NAME and ODQ. Therefore, coronary vasodilator effect elicited by V. album L. aqueous extract is mediated by the NO/sGC pathway.
