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Nitric oxide modulates renal vasoconstrictor effect of endothelin-1 in conscious lambs

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Abstract

To test the hypothesis that nitric oxide (NO) buffers the renal vasoconstrictor effects of endothelin-1 (ET-1) early in life, renal haemodynamic responses to ET-1 were measured in the presence and absence of endogenously produced NO in conscious lambs. Renal haemodynamic effects of ET-1 were measured for 5 min before (control) and 20 min after intraarterial injection of ET-1 before and after pretreatment with 20 mg/kg of the l-arginine analogue NG-nitro-l-arginine methyl ester (l-NAME), (experiment 1) and its inactive isomer D-NAME (experiment 2) in conscious lambs aged ~1 week (N=7) and ~6 weeks (N=6). The two experiments were carried out in random order at intervals of 24–48 h. In lambs aged ~6 weeks, a marked increase in renal vascular resistance (RVR) was elicited by ET-1 administration; this response was enhanced twofold following pretreatment with l-NAME. In 1-week-old lambs, however, an increase in RVR in response to ET-1 occurred only after pretreatment with l-NAME. Therefore, we accept our hypothesis and conclude that NO buffers the renal vasoconstrictor effects of ET-1 early in life.

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Acknowledgements

A portion of this work was presented as a poster at the annual meetings for Experimental Biology 2002 and published in the proceedings [Smith FG, van der Velde L, Sener A (2002) Nitric oxide buffers renal vasoconstrictor effects of endothelin-1 in conscious newborn lambs. FASEB J 15:A331]. Operating grants provided by the Canadian Institutes for Health Research and the Kidney Foundation of Canada supported this research. During the tenure of these experiments, Dr. Francine G. Smith was a Heritage Medical Senior Scholar supported by the Alberta Heritage Foundation for Medical Research, and Dr. Alp Sener was supported by a PMAC/MRC graduate studentship.

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Authors and Affiliations

  1. Departments of Physiology & Biophysics/Medicine, University of Calgary, Calgary, Alberta, Canada

    Francine G. Smith, Liesbeth van der Velde & Alp Sener

Authors
  1. Francine G. Smith
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  2. Liesbeth van der Velde
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  3. Alp Sener
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Correspondence to Francine G. Smith.

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The current address of Dr. Liesbeth van der Velde is UCLA Medical Center, Los Angeles, CA, USA. The current address of Dr. Alp Sener is University of Western Ontario, London, ON, Canada

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Smith, F.G., van der Velde, L. & Sener, A. Nitric oxide modulates renal vasoconstrictor effect of endothelin-1 in conscious lambs. Pediatr Nephrol 20, 1545–1551 (2005). https://doi.org/10.1007/s00467-005-2015-5

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