Effects of Chronic Eta-Receptor Blockade in Stroke-Prone Spontaneously Hypertensive Rats.
It has been reported that some ET-receptor blockers prevent cerebral injury in stroke-prone spontaneously hypertensive rats (SPSHR), whereas chronic inhibition of nitric oxide synthase (NOS) precipitates stroke. We investigated the protective effects of chronic treatment with BSF208075, a selective ETA-receptor blocker in SPSHR treated with the NOS inhibitor, L-NAME, or untreated. 4 groups of male SPSHR, 10 week old, were studied: a control group and 3 groups treated with BSF208075 (30 mg/kg/day), L-NAME (10 mg/kg/day) or BSF208075+L-NAME (30 and 10 mg/kg/day, respectively). Systolic blood pressure, body weight and survival were recorded. In the control group, severe hypertension (292.3±1.0mmHg; p<0.01 vs baseline) developed within 4 weeks. In contrast, in the BSF208075-treated group, the development of hypertension (265.2±3.8mmHg; p<0.01 vs control) was limited and blood pressure started to decrease after 4 weeks of treatment. In both of these groups, the increase in body weight was normal and similar, and 90% of the animals were still alive after 50 days of treatment. In the L-NAME-treated group, the blood pressure immediately and drastically increased, the body weight was reduced by 50% within 6 weeks of treatment. 50% of mortality was observed after 22 days of treatment, and all rats died within 36 days. The mean survival was 25.9±2.4 days. In L-NAME+BSF208075-treated group, BSF208075, although it did not prevent the development of hypertension, it reduced the loss of body weight and increased mean survival to 36.7±1.4 days (p<0.01 vs L-NAME-treated group). In this group, 50% of mortality was observed after 37 days of treatment, and all rats died within 41 days. These results show that BSF208075 delays the development of hypertension in SPSHR, and increases survival of L-NAME-treated SPSHR, independent of hypertension.