beta-Adrenergic, Angiotensin II, and Bradykinin Receptors Enhance Neurotransmission in Human Kidney

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1995-09, Vol.26 (3), p.445-451
• Main Authors: Rump, Lars C, Bohmann, Christine, Schaible, Ulrike, Schultze-Seemann, Wolfgang, Schollmeyer, Peter J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Angiotensin II - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Biological and medical sciences; Bradykinin - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Humans; Isoproterenol - pharmacology; Kidney - innervation; Male; Middle Aged; Norepinephrine - metabolism; Receptors, Adrenergic, beta - physiology; Receptors, Angiotensin - physiology; Receptors, Bradykinin - physiology; Synaptic Transmission - drug effects; Vertebrates: urinary system
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.26.3.445

The aim of this study was to investigate angiotensin II (Ang II) receptor-, bradykinin receptor-, and beta-adrenergic receptor-mediated modulation of norepinephrine release from human renal sympathetic nerves and to characterize the respective receptor subtypes involved. Human cortical kidney slices were incubated with [() Hydrogen]norepinephrine, placed in superfusion chambers between two platinum electrodes, and superfused with Krebs-Henseleit solution. The sympathetic nerves were stimulated electrically at 2.5 Hz for 1 minute, and the stimulation-induced outflow of radioactivity was taken as an index of endogenous norepinephrine release. Ang II and its precursor Ang I (both 0.01 to 1 microu mol/L) enhanced stimulation-induced outflow of radioactivity in a concentration-dependent manner, with EC50 values of 0.03 and 0.05 micro mol/L, respectively. The enhancement by Ang I but not that by Ang II was inhibited by the angiotensin-converting enzyme inhibitor captopril (3 micro mol/L). The concentration-response curves of Ang I and Ang II were shifted to the right by EXP 3174 (0.01 micro mol), the in vitro active form of the Ang II type 1 receptor antagonist losartan, with affinity estimates of 8.72 and 9.30, respectively. A higher concentration of EXP 3174 (0.1 micro mol/L) abolished the facilitatory effects of Ang I and Ang II. The Ang II type 2 receptor antagonist PD 123319 (10 micro mol/L) did not alter the facilitation by Ang II. In the absence of other drugs, bradykinin (0.01 to 1 micro mol/L) failed to modulate stimulation-induced outflow of radioactivity but in the presence of captopril (3 micro mol/L) enhanced it in a concentration-dependent manner, with an EC50 of 0.1 micro mol/L. This facilitatory effect of bradykinin was prevented by the bradykinin type 2 receptor antagonist Hoe 140 (0.3 micro mol/L). The beta1/beta2 -adrenergic receptor agonist isoproterenol (0.001 to 0.1 micro mol/L) also enhanced stimulation-induced outflow of radioactivity in a concentration-dependent manner, with an EC50 of 0.008 micro mol/L. The facilitatory effect of isoproterenol was abolished by the beta2 -adrenergic receptor antagonist ICI 118551 (0.03 micro moL/L) but unaltered by the beta1 -adrenergic receptor antagonist atenolol (3 micro mol/L), captopril (3 micro mol/L), or EXP 3174 (0.1 micro mol/L). We conclude that activation of prejunctional Ang II type 1, bradykinin type 2, and beta2 -adrenergic receptors facilitates renal norepinephrine release in humans. Ang I