Mechanism of norepinephrine release elicited by renal nerve stimulation, veratridine and potassium chloride in the isolated rat kidney
el-Din, M.M.; Malik, K.U.
Journal of Pharmacology and Experimental Therapeutics 243(1): 76-85
1987
ISSN/ISBN: 0022-3565 PMID: 3668868 Document Number: 298161
We have investigated the mechanism by which renal nerve stimulation (RNS), veratridine (Vt) and KCl promote release of norepinephrine in the isolated rat kidney perfused with Tyrode's solution and prelabeled with [3H]norepinephrine by examining the overflow of tritium elicited by these stimuli during 1) extracellular Ca++ depletion, 2) alterations in extracellular Na+ concentration and 3) administration of tetrodotoxin, amiloride, LiCl and calcium channel blockers. RNS (1-4 Hz), Vt (15-90 nmol) and KCl (150-500 .mu.mol) produced renal vasoconstriction and enhanced the tritium overflow in a frequency- and concentration-dependent manner, respectively. Omission of Ca++ (1.8 mM) from the perfusion liquid abolished that the renal vasoconstriction and the increase in tritium overflowed elicited by RNA and KCl and substantially reduced that caused by Vt. Lowering the Na+ concentration in the perfusion medium (from 150 to 25 nM) reduced the overflow of tritium and the renal vasoconstriction caused by RNS (2 Hz) or VT (45 nmol); the increase in tritium overflow in response to these stimuli was positively correlated with extracellular Na+ (25-150 mM). In contrast, KCI-induced tritium overflow was negatively correlated with extracellular Na+ concentration. Tetrodotoxin (0.3 .mu.M) abolished the effect of RNS and Vt, but not that of KCl, to increase overflow of tritium and to produce renal vasoconstriction. Administration of amiloride (180 .mu.M) enhanced the overflow of tritium but attenutated the associated renal vasoconstriction produced by RNS, Vt and KCl. Replacement of NaCl (75 mM) with equimolar concentration of LiCl enhanced the overflow of tritium elicited by RNS, Vt and KCI; the associated renal vasoconstriction remained unaltered. Administration of Ca++ channel blocker, flunarizine (2 .mu.M), but not dilitazem (6 .mu.M) or nifedipine (1.4 .mu.M), inhibited RNS-, Vt- and KCI-induced overflow of tritium; nifedipine enhanced whereas diltiazem failed to alter tritium overflow elicited by these stimuli. The renal vasoconstriction produced by RNS, Vt and KCl was inhibited by diltiazem and nifedipine, produced by RNS, Vt and KCl was inhibited by diltiazem and nifedipine, as well as by flunarizine. These data suggest that RNS, Vt and KCl enhance release of the adrenergic transmitter by promoting influx of Ca++ into the nerve terminal, not by Na+-Ca++ exchange transport process, but rather through specific Ca++ channels that are distinct from those located in the vascular smooth muscle.