HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/F590    most recent 90703.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Inscho, E. W. Articles by Jin, L.-M. Search for Related Content PubMed PubMed Citation Articles by Inscho, E. W. Articles by Jin, L.-M.

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

Department of Physiology, Medical College of Georgia, Augusta, Georgia

Submitted 21 November 2008 ; accepted in final form 5 January 2009

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, , 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 P2X₁ receptor agonists.

P2 receptors; P2X₁ receptors; ATP; Y-27632; autoregulation