Chloride is essential for contraction of afferent arterioles after agonists and potassium

Abstract

A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses to norepinephrine, angiotensin II (ANG II), and potassium were measured after chloride depletion and compared with controls. Chloride depletion did not change arteriolar diameters, but the response to norepinephrine was markedly reduced when chloride was substituted with gluconate (n = 6) or isethionate (n = 6). Reintroduction of chloride fully restored the sensitivity to norepinephrine. Contractions after ANG II and potassium were totally abolished in the absence of chloride (n = 6). In additional experiments (n = 7), the arteriolar contraction to 100 mM potassium was abolished only 1 min after removal of extracellular chloride. We conclude that norepinephrine and ANG II use different mechanisms for contraction and that extracellular chloride is essential for contraction in afferent arterioles after activation of voltage-dependent calcium channels. We suggest that a chloride influx pathway is activated concomitantly with the voltage-dependent calcium channel to allow chloride influx to compensate for the cation influx.

Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange

“…The peak [Ca 2ϩ ] i response was reduced to 71 Ϯ 12 nM, and the plateau was reduced to 23 Ϯ 7 nM (n ϭ 9, peak P ϭ 0.01 and plateau P Ͻ 0.05 vs. control; Fig. 5 (28).…”

“…As (19,30). Functional support for this premise was provided by experiments in which removal of Cl Ϫ from the bath abolished the contractile response to ANG II in microperfused rabbit arterioles (28). In studies of renal blood flow, intrarenal infusion of the nonselective Cl Ϫ channel blocker 4,4-diiosthioyanostilbene-2,2Ј disulfonic acid (DIDS), but not IAA-94 or niflumic acid (NFA), inhibited the vasoconstrictor response to ANG II (50).…”

Ionic mechanisms and Ca2+ handling in airway smooth muscle

“…Now recognising reverse-mode NCX as another voltage-dependent Ca 2+ influx pathway, the current authors would re-evaluate those earlier data; future studies examining Ca 2+ handling and EC coupling should not overlook the potential for Ca 2+ influx via the NCX. sequestration into saponin-permeabilised gastrointestinal smooth muscle cells [144], and depletion of Cl -i reduced angiotensin II-and norepinephrine-induced contractions of vascular smooth muscle [147]. Recently, the current authors reported that the depletion of Cl -i through prolonged bathing in Cl --free bathing solution significantly reduced successive agonist-induced contractions in ASM [148]; additionally, the rates of contraction and relaxation (following agonist removal) were greatly reduced when Cl -i was reduced, suggesting the release and reuptake of Ca 2+ were both hindered by depletion of Cl Altogether, then, there is a growing body of evidence to suggest that the burst of Ca…”

Attenuated renovascular constrictor responses to angiotensin II in adenosine 1 receptor knockout mice

“…Mice (18-26 g) of either sex were used in the study. The method of isolation and perfusion was a modification of that used by Weihprecht et al (18) and Jensen et al (9). Afferent arterioles were microdissected at 4°C from slices of mouse kidneys.…”