Role of prostanoids in the increased vascular responsiveness and delayed tachyphylaxis to serotonin in the kidney of spontaneously hypertensive rats

Abstract

The isolated and perfused kidney of the spontaneously hypertensive rat (SHR) exhibits an increased vascular reactivity and a delayed tachyphylaxis to serotonin (5-hydroxytryptamine) when compared with normotensive Wistar-Kyoto (WKY) rats. Experiments were designed to determine the involvement of products of cyclooxygenase in the augmented response and delayed tachyphylaxis to serotonin in the SHR kidney. Kidneys taken from male, 4-month-old SHR and WKY rats were studied in parallel and perfused with Tyrode's solution at constant, optimal flow rates. Vasoconstrictor responses were recorded as increases in perfusion pressure. The vasoconstrictor responses to serotonin, norepinephrine and angiotensin II were exaggerated in the SHR kidney compared with that of the WKY rat. Indomethacin did not affect the responsiveness to serotonin in the kidney of the SHR but increased the responses to the higher doses of the monoamine in the kidney of the WKY rats. Indomethacin accelerated the tachyphylaxis to serotonin in the SHR but delayed it in the WKY rats. Dazoxiben did not alter the responses to serotonin in the SHR. Responses to norepinephrine in the kidneys from both strains were not affected by indomethacin. The inhibitor of cyclooxygenase reduced the responses to angiotensin II in the kidneys from both hypertensive and normotensive animals. The basal and stimulated (serotonin, norepinephrine and angiotensin II) release of prostaglandins were measured by radioimmunoassay. The basal release of prostacyclin was lower, but that of thromboxane A 2 higher, in the kidneys of SHR compared with those of WKY rats. These experiments suggest that a reduced release of vasodilator prostanoid and the increased release of a vasoconstrictor product of cyclooxygenase may contribute to the increased responsiveness and the delayed tachyphylaxis, respectively, to serotonin in the SHR kidney.