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 autore gulation. Local interstitial infiltration of Ca2+ channel blockers inc reases glomerular pressure and markedly reduces vascular responsivenes s of the tubuloglomerular feedback mechanism. Ca2+ channel blockers se lectively attenuate the afferent vasoconstrictor responses to increase s in perfusion pressure. Although both afferent and efferent arteriole s constrict in response to angiotensin II (Ang II); afferent but not e fferent constriction requires Ca2+ influx through L-type Ca2+ channels . Sensitivity of the preglomerular arterioles to Ang II is also hetero geneous with the greatest sensitivity in glomerulus-near, terminal seg ments. Adenosine triphosphate (ATP) is a vasoconstrictor agonist that selectively activates Ca2+ entry pathways in afferent arterioles but h as no effect on efferent arterioles. In isolated preglomerular smooth muscle cells, increasing extracellular [KCl] increases intracellular C a2+ by stimulating voltage-dependent Ca2+ influx. Ang II, norepinephri ne, and ATP also elicit similar increases in intracellular Ca2+. Mecha nical and agonist-induced voltage-dependent Ca2+ influx is thus a prim ary pathway in the control of cytosolic Ca2+ in afferent arterioles. E fferent arterioles, however, rely primarily on intracellular Ca2+ mobi lization and other Ca2+ influx pathways.