Prevention of hypertension abrogates early inflammatory events in the retina of diabetic hypertensive rats.
Hypertension is an important risk factor associated with development and progression of diabetic retinopathy (DR). The mechanisms by which hypertension increases the risk for DR are poorly understood. As the inflammatory mechanisms play a pivotal role in the pathogenesis of DR, in the present study, we investigated the effects of diabetes, hypertension, and combination of diabetes and hypertension on early inflammatory phenomena in the retina, and the effects of blood pressure control on retinal inflammation. Four-week-old spontaneously hypertensive rats (SHR) and their normotensive counterpart Wistar Kyoto (WKY) rats were rendered diabetic by intravenous injection of streptozotocin. Diabetic SHR rats were randomized to receive no antihypertensive drug (Sd), an antihypertensive drug that acts on renin-angiotensin system (losartan, Sd+Los), or antihypertensive drug that do not affect renin-angiotensin system (triple therapy, Sd+Tri). After 20 days, rats were sacrificed and the retinas were collected. The number of immunohistochemically detected ED1/microglial positive cells and the expression of ICAM-1 in the retina were significantly higher in diabetic SHR than in control SHR (p=0.003). The NF-kappaB p65 levels were higher in SHR compared with WKY groups (p=0.001) and its increment in diabetic SHR was not significant. These abnormalities in diabetic SHR rats were completely prevented by both types of antihypertensive drugs. The concomitance of diabetes and hypertension leads to exuberant inflammatory response in the retina, and the prevention of hypertension abrogates these abnormalities. It is suggested that the inflammatory events may be involved in the mechanism by which hypertension exacerbates retinopathy in patients with diabetes.
Silva
Kamila C
KC
Renal Pathophysiology Laboratory, Nephrology Unit, Faculty of Medical Sciences (FCM), State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Pinto
Camila C
CC
Biswas
Subrata K
SK
Souza
Denise S
DS
de Faria
José B Lopes
JB
de Faria
Jacqueline M Lopes
JM
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000276:immunology; D003930:Diabetic Retinopathy / Q000276:immunology*; D004338:Drug Combinations; D005136:Eye Proteins / Q000032:analysis; D006830:Hydralazine / Q000008:administration & dosage; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000517:prevention & control*; D007150:Immunohistochemistry / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D017628:Microglia / Q000276:immunology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012110:Reserpine / Q000008:administration & dosage; D012160:Retina / Q000276:immunology*; D051996:Transcription Factor RelA / Q000032:analysis
D000959:Antihypertensive Agents; D004338:Drug Combinations; D005136:Eye Proteins; D051996:Transcription Factor RelA; D006852:Hydrochlorothiazide; D018799:Intercellular Adhesion Molecule-1; D006830:Hydralazine; D012110:Reserpine; D019808:Losartan