Nitric oxide synthase blockade and renal vascular responses to norepinephrine and endothelin-1 in conscious dogs

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Abstract

The effects of inhibiting nitric oxide (NO) syn-thase with NG-nitro-L-arginine (L-NNA) on renal vasoconstrictor responses to intrarenally administered norepi-nephrine (NE) and endothelin-1 (ET-1) were studied in conscious dogs. NE was infused into the renal artery at 0.02, 0.05, 0.1, and 0.2 μg/kg/min (15 min at each rate), with the dogs (n = 5) pretreated with either L-NNA 10 mg/kg intravenously (i.v.) or vehicle (250 mM NaHCO3 solution at 2 ml/kg i.v.) NE produced dose-related decreases in renal blood flow (RBF) and renal vascular conductance that were significantly greater after L-NNA pre-treatment than after vehicle. ET-1 was infused intrarenally at 2.7 ng/kg/min for 45 min with the dogs (n = 5) pretreated with either L-NNA 10 mg/kg i.v. or vehicle. ET-1 caused a progressive decrease in RBF and renal vascular conductance. In contrast to the results with NE, RBF and renal vascular conductance decreased significantly less in response to ET when the dogs were pretreated with L-NNA as compared with pretreatment with vehicle. Therefore, blockade of NO synthase augmented NE-induced but not ET-induced renal vasoconstriction. The results therefore suggest that NO may act to lessen the renal vascular effects of NE, but this effect does not appear to be generalised to all vasoconstrictors.

Original languageEnglish
Pages (from-to)979-985
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume25
Issue number6
Publication statusPublished - 1995
Externally publishedYes

Keywords

  • Conscious dog
  • Endothelin-1
  • Kidney
  • N<sup>G</sup>-Nitro-L-arginine
  • Nitric oxide
  • Norepinephrine

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