There is evidence that cyclooxygenase products of arachidonic acid participate in the control of renin release. In this study we tested the hypothesis that prostaglandin (PG) I2 and/or its metabolite(s), which are synthesized in the afferent arteriole (AF), stimulate renin release by acting directly on the AF while PGE2 stimulates renin release indirectly via the macula densa. AF alone and AF with macula densa attached (AF-MD) were microdissected from rabbit kidneys and incubated in vitro. The renin release rate from a single AF (or an AF-MD) was calculated and expressed as ng AI·hr-1 AF-1/hr (where AI is angiotensin I). When arachidonic acid (0.12 mM) or PGI2 (10 μM) was added to AF, renin release increased significantly (P < 0.0001) from 1.04 ± 0.21 to 3.12 ± 0.86 (X̄ ± SEM, N = 7) and from 0.45 ± 0.14 to 1.48 ± 0.53 (N = 9), respectively. During the recovery period, renin release increased even further, reaching 9.53 ± 1.76 and 4.50 ± 1.24, respectively. A PGI2 synthetase inhibitor, 9,11-azoprosta-5,13-dienoic acid blocked the effect of arachidonic acid. To examine whether the increases in renin release during the recovery period were due to metabolite(s) of PGI2, we tested the effect of both 6-keto-PGE1 (an active metabolite of PGI2) and carba-PGI2 (a synthetic analog that is metabolized differently from PGI2). Six-keto-PGE1 and carba-PGI2 increased renin release only during the experimental period with no further increase during the recovery period. When PGE2 (14 μM) was added to AF alone, renin release did not change significantly; however, when it was added to AF-MD, renin release increased by 133%, going from 0.54 ± 0.09 to 1.26 ± 0.24 (N = 8, P < 0.02). These results suggest that AF synthesizes PGI2 and possibly its metabolite(s), which in turn stimulate renin release by acting directly on AF, whereas PGE2 stimulates renin release indirectly via the macula densa.
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