Endothelin and the Kidney

  • Winifred G. Nayler


As soon as the structure and basic properties of endothelin-1 had been determined investigators began studying its effect on specific organs. The kidneys, the brain and the heart were natural targets for attention. As far as the kidneys are concerned it soon bacame apparent:
  1. (i)

    that renal arteries are particularly sensitive to the polypeptide — more sensitive even than the systemic vasculature (Pernow et al. 1989c)

  2. (ii)

    that the kidney contains specific high affinity binding sites for the polypeptide (Jones et al. 1989a; Kohzuki et al. 1989);

  3. (iii)

    that the distribution of these binding sites throughout the kidney is non-homogeneous (Kohzuki et al. 1989; Davenport et al. 1989b);

  4. (iv)

    that the kidney contains mRNA for endothelin-1 and accordingly is capable of synthesizing the polypeptide (MacCumber et al. 1989), and

  5. (v)
    that when injected into the renal artery, endothelin-1:
    1. (a)

      reduces renal blood flow

    2. (b)

      increases renal artery resistance

    3. (c)

      slows glomerular filtration

    4. (d)

      reduces urinary sodium excretion, and

    5. (e)

      stimulates prostaglandin E2 and I2 release (Miura et al. 1989). In addition

    6. (f)

      whereas high doses of endothelin-1 increase renal arterial resistance, low doses can cause dilation (Lippton et al. 1988; Figure 11.1). Under in vivo conditions, therefore, the response is often biphasic, with a transiet elevation of renal blood flow followed by a gradual but sustained fall (Nakamoto et al. 1989). Finally

    7. (vi)

      the constrictor effect of endothelin-1 on the renal vasculature, and particularly the afferent arterioles, is markedly attenuated by the dihydropyridine-based calcium antagonists (Loutzenhiser et al. 1990).



Renal Artery Atrial Natriuretic Peptide Mesangial Cell Renal Blood Flow Urinary Sodium Excretion 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • Winifred G. Nayler
    • 1
  1. 1.Department of Medicine Austin and Repatriation HospitalThe University of MelbourneHeidelbergAustralia

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