Carvedilol protects the peritubular capillaries and kidney structure in spontaneously hypertensive rats

G CAO; H GÓMEZ LLAMBÍ; G OTTAVIANO; MULLER A; J MILEI

INTERNATIONAL JOURNAL OF CARDIOLOGY

ELSEVIER IRELAND LTD

Lugar: Ireland; Año: 2014

0167-5273

Carvedilol protects the peritubular capillaries and kidney structure inspontaneously hypertensive ratsCarvedilol improves autoregulation of renal blood flow by virtue ofits ability to reduce intrarenal vascular resistance [1] and modify thevascular reactivity in non-denervated kidney [2]. Long-term changesin renal blood flow, for example during essential hypertension, may induceprogressive modifications in the microvascular (MV) tone, giventhat the chronic vascular constriction can lead to peritubular capillaryloss and increased intrarenal vascular resistance. The severity of thesechanges may affect the kidney functions, a phenomenon known as vascularrarefaction [3]. Carvedilol is a beta blocker with antioxidant andvasodilating activities, which has proven to provide renal protection inexperimental rat models, beyond their antihypertensive activity [4].However, little is known about the potential preventive role of carvedilolon MV remodeling in spontaneously hypertensive rats (SHR). Eightweek-old male SHR and Wistar-Kyoto (WKY) rats were randomlydivided into three groups: SHR (n = 10), SHR-C (n = 10; carvedilol20 mg/kg/day) and WKY (n = 10). For 16 months, animals were fedon a standard commercial chow (Cooperación, Buenos Aires, Argentina)ad libitum and housed inside an indoor laboratory facility with a12 h light/dark cycle. At 18 months of age, all the rats were sacrificedand the kidneys excised and processed for quantitative microscopyand immunohistochemistry studies. Animal care was according tothe ?Guide for the Care and Use of Laboratory Animals? published bythe US National Institutes of Health (NIH publication no. 85-53, revised1998). At baseline and after every 2 weeks, systolic blood pressure(SBP) was measured by tail-cuff plethysmography. Blood samples wereobtained by ventricular puncture and the plasmatic levels of creatininewere assessed with a commercial kit (Sigma Chemical Co., St. Louis,MO). The animals were euthanized under anesthesia and the kidneyswere removed, weighed, fixed in 10% buffered formaldehyde andprocessed for histology. Thin sections from tissue blocks werestained with periodic acid-Schiff (PAS), Masson´s trichrome (MT)and Jones methenamine (JM), and the glomerular profile numerical densityper area [NA (glom) per mm2], glomerular volume (VG, expressed inμm3),mesangialmatrix (MM, expressed in percentage), tubular metaplasia(TM, expressed in % of glomeruli), interstitial fibrosis (IF, expressed inpercentage) and tubular atrophy (TA, expressed in percentage) wereevaluated by using an image processing software (Image-Pro Plus version6; Media Cybernetics, Silver Spring, Maryland, USA). The integrated opticaldensity (IOD) [5] was employed to assess the immunohistochemicallabeling that allowed to estimate: peritubular capillary density (PCD, endothelialimmunostaining for CD34), peritubular capillary protection(TVEGF, tubular staining for vascular endothelial growth factor), apoptosis(tubular expression for caspase-3) and oxidative stress status (tubular expressionfor: thioredoxin-1 (Ttrx1) and peroxiredoxin-2 (Tprx2)). The normalizedtotal kidney mass (KMT)was estimated for comparison purposes.A significant reduction of total kidney mass was demonstrated inSHR-C (−23.7% vs WKY and −15.83% vs SHR). Also, animals treatedwith carvedilol showed an elevated NA (glom) and VG compared toSHR (+16.64% and+29.21%, respectively),whileMMwas significantlydecreased (−38.94%). In addition, carvedilol induced a significant reductionin TA and IF compared to SHR (−54.66% and−61.08%, respectively