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Vasoconstrictor-induced heterologous down-regulation of vascular atrial natriuretic peptide receptor

Y Hirata1, T Emori, K Ohta

  • 1Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.

European Journal of Pharmacology
|May 30, 1989
PubMed

Insights

Vasoconstrictors like angiotensin reduce atrial natriuretic peptide (ANP) receptors in smooth muscle cells. This down-regulation, linked to protein kinase C activation, impairs ANP signaling.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Pharmacology
  • Cell Signaling

Background:

  • Atrial natriuretic peptide (ANP) plays a crucial role in regulating vascular tone and blood pressure.
  • Vascular smooth muscle cells (VSMCs) express ANP receptors that mediate ANP's biological effects.
  • Receptor regulation is critical for maintaining cellular responsiveness to signaling molecules.

Purpose of the Study:

  • To investigate the effect of prolonged vasoconstrictor treatment on atrial natriuretic peptide (ANP) receptor expression and function in cultured rat VSMCs.
  • To explore the role of protein kinase C (PKC) in the down-regulation of ANP receptors induced by vasoconstrictors.
  • To determine the functional consequences of ANP receptor down-regulation on ANP-stimulated cyclic GMP (cGMP) accumulation.

Main Methods:

  • Primary cultures of rat aortic smooth muscle cells were pretreated for 24 hours with angiotensin and vasopressin.
  • Maximal binding capacity of ANP receptors was assessed using radioligand binding assays.
  • ANP-stimulated cGMP accumulation was measured in response to peptide stimulation.
  • The effect of phorbol ester, a known PKC activator, was used as a comparative model.

Main Results:

  • Long-term pretreatment with angiotensin and vasopressin significantly reduced the maximal binding capacity of ANP receptors in VSMCs.
  • This reduction in ANP receptor binding was comparable to the effect observed with phorbol ester.
  • The down-regulation of ANP receptors by vasoconstrictors and phorbol ester was associated with a marked attenuation of ANP-stimulated cGMP production.
  • These findings indicate a functional impairment in ANP signaling following receptor down-regulation.

Conclusions:

  • Vasoconstrictors, such as angiotensin and vasopressin, induce heterologous down-regulation of vascular ANP receptors.
  • Activation of protein kinase C (PKC) by vasoconstrictors is implicated in the mechanism of ANP receptor down-regulation.
  • The observed down-regulation of ANP receptors leads to impaired ANP-mediated signaling, specifically reduced cGMP accumulation.

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