Enhanced thromboxane A2 biosynthesis in the kidney of spontaneously hypertensive rats during development of hypertension

Arachidonic acid (AA)-induced pressor response and production of thromboxane YXB₂, the stable metabolite of TXA₂, prostaglandin (PG)-like substance (PLS) and 6-keto-PGF_1α the stable metabolite of prostacyclin (PGI₂), were studied using isolated, perfused kidneys of 6- and 18-week old spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), two-kidney, one clip hpertensive rats (RHR) and DOCA/salt hypertensive rats (DOCA/salt HR). The AA-induced pressor response and release of TXB₂ were highest in the 6-week old SHR, whereas, the release of PLS and 6-keto-PGF_1α was marked in the 18-week old SHR and the established hypertensive stages of both RHR and DOCA/salt HR. In the kidneys of SHR and WKY, exogenous TXA₂ induced a severe vasoconstriction and there was a positive correlation between the AA-induced pressor response and the release of TXB₂ or PLS. Thus, the initiation of hypertension in SHR may follow an accelerated synthesis of TXA₂ against PGI₂ in response to stimuli which induce a release of AA.