ANGIOTENSIN-II-STIMULATED RELEASE OF THROMBOXANE-A2 AND PROSTACYCLIN (PGI2) IN ISOLATED, PERFUSED KIDNEYS OF SPONTANEOUSLY HYPERTENSIVE RATS

Angiotensin-II(A-II)-stimulated release of rabbit aorta-contracting substance (RCS), prostaglandin-like substance (PLS) and dog coronary-relaxing substance (DRS) was studied in isolated, perfused kidneys of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). When the perfusion pressure was set at 60-70 mmHg, the dose-related pressor response of the kidney to A-II did not differ significantly between the strains, or between the ages of 6, 12 and 18 weeks. The A-II-induced release of RCS from the kidney was most remarkable in 6-week SHR, slight in 12- and 18-week SHR, but negligible for all ages of WKY. The DRS release was remarkable in 12- and 18-week SHR, but was hardly detectable in 6-week SHR and all ages of WKY. The PLS release was much more remarkable in 18-week SHR than in 6- and 12-week SHR and all ages of WKY. The RCS was confirmed to be thromboxane A2 (TXA2) by: (1) its half-life of 38 sec at 37°, (2) a concomitant release of radio-immunoassayable TXB2: (a stable metabolite of TXA2) into the perfusate and (3) specific inhibition of its release by L-8027 (a TXA2 synthetase inhibitor). The DRS was considered to be prostacyclin (PGI2) by: (1) its half-life of 5.2 min at 37° and (2) its anti-platelet aggregation activity. It is speculated that an enhanced TXA2 synthesis in the 6-week SHR kidney may be involved in increasing the renal vascular resistance and in initiating the process of hypertension. © 1979.