SHORT‐TERM TREATMENT OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS WITH AN AT1 RECEPTOR BLOCKER PROTECTS AGAINST HYPERTENSIVE END‐ORGAN DAMAGE BY PROLONGED INHIBITION OF THE RENIN–ANGIOTENSIN SYSTEM

Abstract

The aim of the present study was to investigate the effects of short-term treatment with an AT(1) receptor blocker (ARB) on amelioration of hypertensive end-organ damage in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP were divided into two groups: (i) an ARB-treated group; and (ii) a control group. Candesartan (1 mg/kg per day) was administered orally from 6 to 11 weeks of age. At 20 weeks of age, plasma renin activity (PRA), angiotensin II concentrations, angiotensin-converting enzyme (ACE) activity and hydroperoxide content were measured. Expression of intercellular adhesion molecule (ICAM)-1, renin, AT(1) and AT(2) receptors was investigated by reverse transcription-polymerase chain reaction. Blood pressure in the ARB group was slightly lower at 7, 8, 11, 13-15 and 18 weeks of age, but no significant difference in blood pressure was found between the ARB and control groups at 20 weeks of age. All rats in the control group had cerebral oedema, whereas no lesions were found in the ARB group. In the ARB group, PRA, AII and hydroperoxide content were lower than in the control group. In the ARB-treated group, lower ICAM-1 expression was found in the cerebral cortex and slightly, albeit not significantly, lower expression of renin was found in the kidney. In contrast, AT(1) receptor expression in the cerebrum and kidney was higher in the ARB group compared with the control group. These results indicate that short-term treatment of SHRSP with ARB at a young age is effective in preventing cerebral oedema after maturation. Such beneficial effects of ARB may be due, in part, to decreased blood pressure and is likely mainly due to inhibition of total circulating and local renin-angiotensin systems.