Renal microvascular constriction to membrane depolarization and other stimuli: pivotal role for rho-kinase.
Contraction of vascular smooth muscle is determined not only by levels of intracellular free calcium but also by the sensitivity of its contractile apparatus. A potential modulator of the latter is rho-kinase. We addressed the question of a possible central role for rho-kinase in the regulation of periglomerular microvascular tone. In the rat hydronephrotic kidney model, diameter changes of distal interlobular arteries, afferent and efferent arterioles were measured using three distinctly different stimuli: intravascular pressure changes, angiotensin II (AngII) and membrane depolarization, which is a physiological component of many signaling pathways, as evoked in two ways. Two selective, structurally different rho-kinase inhibitors, Y-27632 and HA-1077, were employed, as well as a selective protein kinase C alpha inhibitor. Preglomerular vasoconstriction induced by direct membrane depolarization, increases in pressure or AngII all depended for their effect on rho-kinase. A differing role for rho-kinase in efferent arteriolar constriction to AngII as compared to preglomerular microvessels was not found. In conclusion, our data indicate that in the kidney, rho-kinase is involved in a variety of signaling pathways leading to microvascular constriction. It plays a pivotal role not only in preglomerular but also in postglomerular tone.
Roos
Marjon H
MH
Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Van der Boechorstraat 7, 1081 BT, Amsterdam, The Netherlands.
van Rodijnen
William F
WF
van Lambalgen
Anton A
AA
ter Wee
Piet M
PM
Tangelder
Geert Jan
GJ
D000818:Animals; D006869:Hydronephrosis / Q000503:physiopathology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008833:Microcirculation / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology*; D014661:Vasoconstriction; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases