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      Effect of Radiocontrast Agents on Intrarenal Nitric Oxide (NO) and NO Synthase Activity

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          Background/Aims: Contrast media (CM) induce a biphasic renal hemodynamic response, with late prominent cortical vasoconstriction and marked outer medullary vasodilation. The objective of the study was to explore a possible role for altered nitric oxide (NO) production or bioavailability in these hemodynamic responses. Methods: We explored the impact of CM (sodium iothalamate) upon rat renal NO synthase (NOS) activity (citrulline recovery) and NO (using a NO electrode). Results: The cortical NOS activity following CM was 11.5 ± 1.0 versus 13.8 ± 1.1 nmol/gww/min (gww = gram wet weight) in controls (p = 0.16, NS). In rats pretreated with the nonselective endothelin antagonist bosentan, CM reduced the cortical NOS activity to 8.5 ± 1.2 nmol/gww/min (p < 0.005 vs. controls). Cortial NO readings declined over 30 min following CM by 13 ± 8% (p < 0.05, Anova), in parallel with the decline in cortical blood flow. The outer medullary NOS activity was not affected by CM (5.2 ± 1.5 vs. 5.5 ± 1.3) nmol/gww/min in controls) or bosentan. Nevertheless, the outer medullary NO reading increased by 36 ± 23% (p < 0.05), with a concomitant increase in regional blood flow. Conclusion: In the cortex, CM might reduce the NOS activity (an effect blunted by endothelin release). This may potentiate the effect of endothelin to induce regional vasoconstriction. In the outer medulla, the vasodilatory response to CM does not seem to be mediated by enhanced NOS activity and might reflect increased local NO bioavailability as the result of regional hypoxia.

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          Practical nitric oxide measurement employing a nitric oxide‐selective electrode

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            Endothelin receptors: receptor classification, novel receptor antagonists, and potential therapeutic targets.

            The development of endothelin receptor antagonists has progressed rapidly since the initial discovery of endothelin. Highly potent, orally active nonpeptide endothelin receptor antagonists have been identified, and are being used as pharmacological tools to elucidate the role of endothelin in pathological disorders. Subtype selective endothelin receptor antagonists will also be useful in understanding the physiological and pathological roles of the different subtypes of the endothelin receptors. The selectivity profile for the ideal endothelin receptor antagonist is presently unknown, and it may actually be that the optimal profile for a compound may depend on the clinical indication. In the near future, data from clinical trials with endothelin receptor antagonists will become available and will help to establish the role of endothelin in the etiology of human disease, as well as to provide valuable information concerning the optimum endothelin receptor subtype selectivity for antagonists needed for therapeutic agents.

              Author and article information

              Nephron Exp Nephrol
              Cardiorenal Medicine
              S. Karger AG
              December 1998
              06 November 1998
              : 6
              : 6
              : 557-562
              a Department of Medicine, Hadassah Hospital Mt. Scopus and Hebrew University Medical School, Jerusalem, and b Nephrology Unit, Bikur Holim Hospital, Jerusalem, Israel
              20571 Exp Nephrol 1998;6:557–562
              © 1998 S. Karger AG, Basel

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              Figures: 2, Tables: 1, References: 38, Pages: 6
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