INHIBITION BY METOPROLOL OF THE ANTIHYPERTENSIVE EFFECT OF ASPIRIN IN YOUNG-RATS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 234  (1) , 166-171
Abstract
A group of 21 day old, spontaneous hypertensive rats (SHR) received either aspirin (75-100 mg/kg), metoprolol (1.0-1.5 mg/kg) or both in their drinking water for 56 days. Controls received plain water. Groups of normotensive Wistar-Kyoto rats (WKY) received the same drug treatment as did the SHR. Blood pressure, heart rate and body weight were determined weekly, and water consumption was monitored on a daily basis. Renal prostaglandin (PG) activities were determined in a separate group of rats at 7 and at 56 days on each protocol. Blood presssures in the SHR remained in the range of the WKY during 56 days of treatment with aspirin or metoprolol, but increased to hypertensive levels after exposure to plain water. Blood pressures in the WKY receiving aspirin or metoprolol were also lower than those receiving plain water, but the antihypertensive effect was somewhat slower in onset. The antihypertensive effects of aspirin and of metoprolol were lost in the SHR, but not in the WKY when both drugs were given simultaneously in the drinking water. In comparison to rats receiving plain water, renal PG activity (PGF1.alpha. and PGF2.alpha.) was lower in rats receiving aspirin, metoprolol or both together. The mechanism for the antihypertensive effect of aspirin in the young SHR may be related to a decline in renal PG content, or to the release of other hormoned controlling water and electrolyte balance. Reports that the cyclooxygenase inhibitors, such as aspirin, can block the antihypertensive effect of the .beta. adrenoceptor antagonists are confirmed in chronic studies using the SHR model. The reason why aspirin loses its antihypertensive effect in the SHR when given in combination with metoprolol is unexplained. As PG activity remained low when both drugs were given together, it is difficult to ascribe the loss of the antihypertensive effect to the PG system.