Influence of acetylsalicylic acid and BM 13177 on blood pressure and efficacy of antihypertensive drugs in spontaneously hypertensive rats.
The effects of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) and of the TXA2 receptor antagonist BM 13177 on blood pressure and on the efficiency of antihypertensive drugs were investigated in spontaneously hypertensive rats (SHR). ASA and BM 13177 applicated once caused a significant, but short-lasting decrease in blood pressure in SHR. In contrast, repeated application of ASA (3 x 100 mg/kg) caused a slight, but significant increase in blood pressure. Pretreatment with BM 13177 (60 mg/kg i.v.) did not influence the antihypertensive effect of the drugs clonidine, propranolol and dihydralazine. Pretreatment of SHR with ASA intensified significantly the effect of these drugs on blood pressure, independent of their mode of action, and on heart rate (dihydralazine). The formation of TXB2 in the aorta thoracica in ASA pretreated SHR 20 min after drug application, was more strongly inhibited than was the formation of PGI2. Therefore the TXA2/PGI2 balance shifted in favor of the latter. However, in normotensive rats, ASA was without any effect on blood pressure and on the antihypertensive efficacy of the drugs. In conclusion it could be suggested that prostanoids are involved in the short term as well as in the long term regulation of the blood pressure and in the blood pressure lowering activity of drugs at least in a hypertensive state.