Comparison of aspirin and indomethacin pre-treatments on the responses to reduced renal artery pressure in conscious dogs.

摘要

To examine the role of prostaglandins in physiologically induced renin release, we reduced renal artery pressure within the autoregulatory range in chronically instrumented conscious dogs with aspirin, indomethacin or no pre-treatment. In untreated dogs, reduction of renal artery pressure to 60 mmHg for 90 min produced rises in plasma renin activity (+ 5.4 +/- 1.0 ng ml.-1 hr-1) and mean arterial pressure (+ 17 +/- 2 mmHg) without significant effect on renal blood flow (n = 13). Aspirin pre-treatment (2 X 25-40 mg kg-1 orally) had no effect on the renin, arterial pressure or renal blood flow responses to renal artery pressure reduction (n = 7). In contrast, indomethacin pre-treatment (2 X 2-3 mg kg-1 orally) significantly lessened the increase in plasma renin activity during reduced renal artery pressure (+ 2.0 +/- 0.3 ng ml.-1 hr-1, n = 11). The relative effectiveness of aspirin and indomethacin in inhibiting prostaglandin production in the kidney was then tested in separate experiments by measuring the renal blood flow responses to renal artery injections of arachidonate (5-200 micrograms kg-1). In the doses used above, aspirin markedly attenuated the blood flow response to arachidonate but indomethacin had almost no effect. Both aspirin and indomethacin abolished the hypotensive effect of intravenous arachidonate (0.5 mg kg-1). These results tentatively suggest that indomethacin may not effectively inhibit renal prostaglandin production in conscious dogs at the doses used in these experiments. Thus the reduced renin release in response to lowered renal artery pressure in indomethacin pre-treated dogs may have been due to another, non-prostaglandin action of indomethacin. The results from the aspirin pre-treated dogs suggest that prostaglandins are not involved in the release of renin in response to reduced renal artery pressure in conscious dogs.