Glomerular Synthesis of Prostaglandins and Thromboxane in Spontaneously Hypertensive Rats

The renal glomerulus converts arachidonic acid to vasoactive prostaglandins and thromboxanes. Since renal vascular resistance is increased in human and experimental hypertension, we have compared the synthesis of prostaglandins and thromboxane B2 in isolated and superfused glomeruli from normotensive and spontaneously hypertensive rats (SHR). We used radioimmunoassay to measure prostaglandins E2, F2α, 6-keto-F1α (a metabolite of prostacyclin) and thromboxane B2 (a metabolite of thromboxane A2). The relative abundance of these compounds was similar in normotensive and hypertensive rats, i.e., prostaglandin F2α > E2 > thromboxane B2 ≃ 6-keto-F11α. In the presence of arachidonic acid, 6.6 μM, the glomeruli from hypertensive rats, aged 6 to 8 months, synthesized twofold more prostaglandin and thromboxane than the glomeruli from normotensive rats, whereas in the absence of added arachidonic acid, there were no significant differences between the prostaglandin synthetic capacity of the glomeruli. Glomerular prostaglandin degradation was not different in SHR compared to Wistar-Kyoto (WKY) rats. Increased glomerular synthesis of prostaglandins and thromboxane was also observed in glomeruli from 4- to 5-month-old SHR after stimulation of endogenous release of arachidonic acid in response to the calcium ionophore, A23187. Glomeruli from young SHR, aged 7 to 8 weeks, also showed enhanced production of prostaglandins and thromboxane despite small (20 mm Hg) differences of blood pressure. Prevention of the hypertension by captopril treatment, from the time of weaning, did not eliminate the differences of prostaglandin and thromboxane synthesis. We conclude that SHR glomeruli show a primary increase of prostaglandin and thromboxane synthesis. These increments are the result of increased cyclooxygenase activity and possibly augmented phospholipase activity. Thromboxane may partially account for the increased renal vascular resistance in SHR through direct vasoconstrictor action and prostaglandins may vasoconstrict indirectly through stimulation of renin release and formation of angiotensin.