We performed micropuncture studies to determine the role of thromboxane A₂ in the exaggerated tubuloglomerular feedback (TGF) activity in young spontaneously hypertensive rats (SHR). Glomerular function was assessed by changes in proximal tubular stop-flow pressure (SFP) produced by different rates of orthograde perfusion through Henle's loop. Seven-week-old SHR exhibited an exaggerated TGF activity compared with Wistar-Kyoto rats (WKY) during euvolemia, confirming earlier studies. During control periods, the feedback-induced maximal SFP response (SFP) was greater in SHR (18-19 vs. 12-13 mmHg in WKY), whereas basal SFP and proximal tubular free-flow pressure were similar in both strains. In one series, the thromboxane A₂ agonist U-46619 was added to the tubular perfusate for a final concentration of 10⁶ M. In WKY, SFP was increased by 100% to 26 mmHg. In contrast, SFP in young SHR was unaffected by the thromboxane A₂ agonist. In other animals, the thromboxane synthase inhibitor pirmagrel (50 mg/kg) was injected intravenously to inhibit thromboxane production. In SHR, pirmagrel decreased SFP by 8.5 mmHg and reduced reactivity. Less attenuation was observed in WKY; SFP was reduced by 3 mmHg, whereas reactivity was unchanged. In other studies, tubular perfusion with the thromboxane receptor inhibitor SQ-29548 (10⁶ M) reduced SFP more in SHR (7 vs. 3 mmHg in WKY) and also decreased reactivity more in SHR (2.3 vs. 0.5 mmHg · nl¹ · min¹). Coperfusion of SQ-29548 and U-46619 resulted in an 85% block of the effect of U-46619 on SFP. Tubular perfusion with the agonist U-46619 during thromboxane synthase inhibition markedly enhanced SFP in both strains, with a greater effect in WKY. These results suggest that elevated levels of thromboxane A₂ in young SHR contribute to the exaggerated TGF control of glomerular function in SHR during the developmental phase of hypertension.

genetic hypertension; juxtaglomerular apparatus; glomerular capillary pressure; macula densa; thromboxane inhibition

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