Chloride is essential for contraction of afferent arterioles after agonists and potassium.
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.
Jensen
B L
BL
Institute of Medical Physiology, University of Copenhagen, Denmark.
Ellekvist
P
P
Skøtt
O
O
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology*; D005942:Gluconates / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors
D018118:Chloride Channels; D002712:Chlorides; D005942:Gluconates; D000804:Angiotensin II; D011189:Potassium Chloride; C030691:gluconic acid; D009638:Norepinephrine