Role of thromboxane in control of arterial pressure and renal function in young spontaneously hypertensive rats.
As platelet and renal thromboxane (TX)A2 synthesis are increased in spontaneously hypertensive rats (SHR), we tested the hypothesis that increased renal TXA2 synthesis may cause the reduction in glomerular filtration rate (GFR), renal plasma flow (RPF), and the increase in arterial pressure in SHR of the Okamoto-Aoki strain. A selective inhibitor of TXA2 synthetase (UK 38485) was given acutely, with or without a TXA2 receptor antagonist (EP-092), to 6- to 8-wk-old SHR and age-matched Wistar-Kyoto rats (WKY) and chronically for 5.5 wk to 3.5-wk-old SHR. Inhibition of TXA2, measured by the stable metabolite TXB2, in the acute experiments was greater than 95% in serum and greater than 80% in glomeruli; in the chronic studies, it was greater than 65% in glomeruli. There was no endoperoxide shunting to vasodilatory and natriuretic prostaglandins (PGE2, PGI2) in glomeruli after TXA2 inhibition. Before drug administration, GFR and RPF were reduced and renal vascular resistance (RVR) was increased in SHR. During acute blockade of renal TXA2 synthesis, with or without a TXA2 receptor antagonist, there was no significant change in GFR, RPF, or RVR in WKY and SHR. Inhibition of TXA2 did not affect urine flow or sodium excretion in anesthetized or conscious WKY or SHR. Mean arterial pressure did not fall in treated SHR and WKY. Chronic TXA2 synthesis inhibition did not improve GFR or RPF in SHR, and systolic arterial pressure was not altered. These findings show that enhanced serum and glomerular TXA2 synthesis do not significantly contribute to the reduction in renal function and are not essential for the development of hypertension in young SHR.
D000818:Animals; D001794:Blood Pressure; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D013997:Time Factors; D014655:Vascular Resistance
D007093:Imidazoles; C039242:dazmegrel; D013928:Thromboxane A2