Demonstration of the existence of nitric oxide-independent as well as nitric oxide-dependent vasodilator mechanisms in the in situ renal circulation in near term pregnant rats

Z.M. Chu, Lawrence Beilin

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    Abstract

    1 We have investigated the role of endogenous nitric oxide on renal vascular reactivity in late pregnancy in in situ blood perfused kidneys of alpha-chloralose anaesthetized Wistar-Kyoto rats. Nitric oxide synthesis inhibition was achieved by intravenous administration of N-G-nitro-L-arginine or N-G-nitro-L-arginine methyl ester.2 Intra-arterial mean blood pressure was lower in pregnancy compared with nonpregnant controls. Following nitric oxide synthesis inhibition mean blood pressure increased in both pregnant and nonpregnant groups, but remained lower in pregnant animals.3 Basal renal perfusion pressure was similar in pregnant and nonpregnant groups. Intravenous administration of N-G-nitro-L-arginine resulted in dose-dependent increases in renal perfusion pressure but responses were substantially depressed in pregnancy.4 Renal vasoconstrictor responses to regional angiotensin II (AII) were decreased in pregnancy, whereas those to noradrenaline (NA) did not differ from nonpregnant controls. N-G-nitro-L-arginine (5 mg kg(-1)) potentiated renal responses to regional AII and NA in both groups, but AII responses remained lower in pregnancy. Blunted renal AII responses in pregnancy were still evident following large doses of N-G-nitro-L-arginine methyl ester (100 mg kg(-1)).5 The results demonstrate that nitric oxide synthesis inhibition increases renal perfusion pressure to a lesser extent in pregnant compared with nonpregnant rats, and that reduced renal presser responses to AII are still evident in pregnancy after nitric oxide synthesis inhibition.6 These results suggest that although endogenous nitric oxide synthesis modulates renal vasoconstrictor responses in both pregnant and nonpregnant animals, this mechanism does not fully account for the blunted renal vasoconstrictor responses to regional AII or nitric oxide inhibitors in near term pregnant rats. The nature of this important physiological vasodilator mechanism in pregnancy remains to be elucidated.
    Original languageEnglish
    Pages (from-to)307-315
    JournalBritish Journal of Pharmacology
    Volume122
    DOIs
    Publication statusPublished - 1997

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