ABNORMALITIES OF THE HIPPOCAMPUS ARE SIMILAR IN DOCA-SALT HYPERTENSIVE RATS AND SPONTANEOUSLY HYPERTENSIVE RATS

PIETRANERA, L; SARAVIA, F; LIMA, A; ROIG, P.; DE NICOLA, AF

Buenos Aires

Congreso; Sociedad Argentina de Biología; 2005

SAB

Hippocampal neuropathology is a recognized feature of the brain of spontaneously hypertensive rats (SHR), but similar studies are lacking in another model of hypertension, the mineralocorticoid-salt treated rats. Our objective was to compare changes in hippocampal parameters in 16 week–old male SHR (BP» 190 mm Hg) and their normotensive Wistar Kyoto controls, with those of male Sprague-Dawley rats receiving (a) 10 mg DOCA every other day during 3 weeks and drinking 1% NaCl solution (BP» 160 mm Hg) and normotensive controls treated with (b) DOCA and drinking water, (c) drinking water only or (d) 1% NaCl only. In these experimental groups we determined: I) cell proliferation in dentate gyrus (DG) using the BrdU labelling technique; II) the number of glial fibrillary acidic protein (GFAP) positive astrocytes under the CA1, CA3 and DG; III) the number of apolipoprotein E (ApoE) positive astrocytes as a marker of potential neuronal damage, and IV) the number of neurons in the hilus of the DG. Changes were remarkably similar in both models: decreased cell proliferation in DG (WKY:55.6±5.55, SHR:31.31±3.28 p<0.01; CTL-H2O: 26.5±2.29, DOCA+SALT: 11.62±1.88 p<0.01 + cells/hemiDG), an increased number of astrocytes immunopositive for GFAP and ApoE (GFAP: CA1: WKY: 142.85±12.40,SHR: 279.54±16.07 p<0.001; CTL-H2O: 120.6±9.29, DOCA+SALT: 201.81±14.80 p<0.001 +astrocytes/mm2). The number of hilar neurons was 37% lower in SHR and DOCA+SALT compared to their normotensive controls. While hypertension may be a leading factor for these abnormalities, endocrine mechanisms may contribute, since hypothalamic-pituitary function, mineralocorticoid receptors and sensitivity to mineralocorticoid treatment are stimulated in SHR, whereas high exogenous mineralocorticoid levels circulate in DOCA-treated rats.  Thus, in addition to the deleterious effects of hypertension, endocrine factors may contribute to the abnormalities of hippocampus in SHR and DOCA-treated rats.