Chloride anion concentration as a determinant of renal vascular responsiveness to vasoconstrictor agents.
1. The role of chloride concentration in modulating vasoconstrictor responses of the rat isolated kidney, perfused with Krebs-Henseleit solution, to angiotensin II (AII), arginine vasopressin (AVP) and phenylephrine (PE) was investigated. 2. Reduction of perfusate chloride from a high (117 mM) to low (87 mM) concentration, by substitution of sodium chloride with a mixture of sodium salts of propionate, acetate and methanesulphonate, reduced responsiveness to all three vasoconstrictors, the change for AII being most pronounced. 3. For AII, reduced vasoactivity with low chloride was evident both in terms of the threshold dose and on the linear part of the dose-response curve but not for the maximum response. This attenuating effect of low chloride on the vasoconstrictor response to AII was reversed when perfusion with high chloride was reinstituted. Continuous perfusion with high chloride progressively increased the vasoconstrictor effect of low doses of AII for successive dose-response curves. 4. In addition to reducing responses on the linear part of the dose-response curve for both AVP and PE, low chloride also reduced the maximum vasoconstrictor response to PE, whereas the threshold dose for the two agonists was unchanged. In contrast to the enhanced pressor response to AII, during continuous perfusion with high chloride, tachyphylaxis occurred with AVP and PE. 5. The ability of chloride to modify renal responsiveness to vasoconstrictor agents may contribute to the increase in renal vascular resistance and decrease in glomerular filtration rate (GFR) which occurs during infusion of hyperchloremic solutions into the renal artery and explain the need for chloride as the anion accompanying sodium in salt-sensitive hypertensive models.
Quilley
C P
CP
Department of Pharmacology, New York Medical College, Valhalla 10595.
Lin
Y S
YS
McGiff
J C
JC
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002712:Chlorides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D010656:Phenylephrine