Rho-kinase inhibition reduces pressure-mediated autoregulatory adjustments in afferent arteriolar diameter

Edward W. Inscho, Anthony K. Cook, R. Clinton Webb, Li Ming Jin

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Abstract

Preglomerular resistance is regulated by calcium influx- and mobilization-dependent mechanisms; however, the role of Rho-kinase in calcium sensitization in the intact kidney has not been carefully examined. Experiments were performed to test the hypothesis that Rho-kinase inhibition blunts pressure-mediated afferent arteriolar autoregulatory behavior and vasoconstrictor responses evoked by angiotensin II and P2X1 receptor activation. Rat kidneys were studied in vitro using the blood-perfused juxtamedullary nephron technique. Autoregulatory behavior was assessed before and during Rho-kinase inhibition with Y-27632 (1.0 μM; n = 5). Control diameter averaged 14.3 ± 0.8 μm and increased to 18.1 ± 0.9 μm (P < 0.05) during Y-27632 treatment. In the continued presence of Y-27632, reducing perfusion pressure to 65 mmHg slightly increased diameter to 18.7 ± 1.0 μm. Subsequent pressure increases to 130 and 160 mmHg yielded afferent arteriolar diameters of 17.5 ± 0.8 and 16.6 ± 0.6 μm (P < 0.05). This 11% decline in diameter is significantly smaller than the 40% decrease obtained in untreated kidneys. The inhibitory effects of Y-27632 on autoregulatory behavior were concentration dependent. Angiotensin II responses were blunted by Y-27632. Angiotensin II (1.0 nM) reduced afferent diameter by 17 ± 1% in untreated arterioles and by 6 ± 2% during exposure to Y-27632. The P2X1 receptor agonist, α, β-methylene ATP, reduced afferent arteriolar diameter by 8 ± 1% but this response was eliminated during exposure to Y-27632. Western blot analysis confirms expression of the Rho-kinase signaling pathway. Thus, Rho-kinase may be important in pressure-mediated autoregulatory adjustments in preglomerular resistance and responsiveness to angiotensin II and autoregulatory P2X 1 receptor agonists.

Original languageEnglish (US)
Pages (from-to)F590-F597
JournalAmerican Journal of Physiology - Renal Physiology
Volume296
Issue number3
DOIs
Publication statusPublished - Mar 1 2009

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Keywords

  • ATP
  • Autoregulation
  • P2 receptors
  • P2X receptors
  • Y-27632

ASJC Scopus subject areas

  • Physiology
  • Urology

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