Heterogeneous activation mechanisms in the renal microvasculature.
Vascular smooth muscle cells in different renal microvascular segments utilize different activation mechanisms to respond to mechanical and vasoactive stimuli. L-type Ca2+ channel blockers vasodilate primarily the preglomerular vascular resistance component responsible for autoregulation. Local interstitial infiltration of Ca2+ channel blockers increases glomerular pressure and markedly reduces vascular responsiveness of the tubuloglomerular feedback mechanism. Ca2+ channel blockers selectively attenuate the afferent vasoconstrictor responses to increases in perfusion pressure. Although both afferent and efferent arterioles constrict in response to angiotensin II (Ang II), afferent but not efferent constriction requires Ca2+ influx through L-type Ca2+ channels. Sensitivity of the preglomerular arterioles to Ang II is also heterogeneous with the greatest sensitivity in glomerulus-near, terminal segments. Adenosine triphosphate (ATP) is a vasoconstrictor agonist that selectively activates Ca2+ entry pathways in afferent arterioles but has no effect on efferent arterioles. In isolated preglomerular smooth muscle cells, increasing extracellular [KCl] increases intracellular Ca2+ by stimulating voltage-dependent Ca2+ influx. Ang II, norepinephrine, and ATP also elicit similar increases in intracellular Ca2+. Mechanical and agonist-induced voltage-dependent Ca2+ influx is thus a primary pathway in the control of cytosolic Ca2+ in afferent arterioles. Efferent arterioles, however, rely primarily on intracellular Ca2+ mobilization and other Ca2+ influx pathways.
Navar
L G
LG
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. navar@mailhost.tcs.tulane.edu
Inscho
E W
EW
Imig
J D
JD
Mitchell
K D
KD
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D007668:Kidney / Q000098:blood supply*; D008833:Microcirculation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000502:physiology; D012079:Renal Circulation / Q000502:physiology*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type