Rho-kinase inhibition reduces pressure-mediated autoregulatory adjustments in afferent arteriolar diameter.
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 microM; n = 5). Control diameter averaged 14.3 +/- 0.8 microm and increased to 18.1 +/- 0.9 microm (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 microm. Subsequent pressure increases to 130 and 160 mmHg yielded afferent arteriolar diameters of 17.5 +/- 0.8 and 16.6 +/- 0.6 microm (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, alpha, beta-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.
Inscho
Edward W
EW
Department of Physiology, Medical College of Georgia, 1120 15th St., Augusta, Georgia 30912-3000, USA. einscho@mail.mcg.edu
Cook
Anthony K
AK
Webb
R Clinton
RC
Jin
Li-Ming
LM
D000577:Amides; D000818:Animals; D001160:Arterioles / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D006706:Homeostasis; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply; D008297:Male; D011312:Pressure; D058910:Purinergic P2 Receptor Agonists; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D014661:Vasoconstriction; D054460:rho-Associated Kinases / Q000502:physiology*
D000577:Amides; D058910:Purinergic P2 Receptor Agonists; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases; D002118:Calcium