Enhancement by locally generated angiotensin II of release of the adrenergic transmitter in the isolated rat kidney

T. Boke, Kafait Malik

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48 Citations (Scopus)

Abstract

In the isolated rat kidney perfused with Tyrode's solution and prelabeled with [3H]norepinephrine, we examined the effect of angiotensin (A)II, AI and synthetic tetradecapeptide (TDP) renin substrate on overflow of tritium in the absence and presence of the inhibitors of the renin-A system to assess the possible modulation by locally generated A of release of the adrenergic transmitter. Infusion of AII (0.3-10 ng/ml), AI (3-30 ng/ml) or synthetic TDP renin substrate (10-100 ng/ml) into the kidney increased perfusion pressure and enhanced the output of tritium and associated rise in perfusion pressure elicited by renal nerve stimulation. The increase in stimulation-induced output of tritium produced by these agents consisted primarily of intact [3H]norepinephrine. AI-converting enzyme inhibitors, SQ 20881 (2 μg/ml) or the diacid form of MK-421 (10 ng/ml), abolished the effect of AI but not that of AII or TDP renin substrate to produce vasoconstriction and to enhance the vascular response and tritium overflow caused by nerve stimulation. The AII competitive antagonist [Sarcosine1-Ala8]AII (1 μg/ml) abolished the facilitatory effects of AII, AI and TDP at the renal vascular adrenergic neuroeffector junction. The effect of a structurally dissimilar peptide, bradykinin, to enhance stimulation-induced renal vasoconstriction and tritium overflow was not altered by [Sarcosine1-Ala8]AII. These data indicate that the facilitatory effect of AI at the renal vascular adrenergic neuroeffector junction is due to its conversion to AII, whereas the effect of TDP renin substrate is due either to its direct conversion to AII or to a direct action on AII receptors at the adrenergic neuroeffector-junction. We conclude that AII generated locally in the kidney may contribute to the regulation of vascular tone by influencing the activity of adrenergic nervous system.

Original languageEnglish (US)
Pages (from-to)900-907
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume226
Issue number3
StatePublished - 1983

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Angiotensin II
Adrenergic Agents
Tritium
Angiotensinogen
Neuroeffector Junction
Kidney
Blood Vessels
Vasoconstriction
Norepinephrine
Teprotide
Perfusion
Pressure
Enalapril
Bradykinin
Enzyme Inhibitors
Renin
Adrenergic Receptors
Nervous System
Peptides

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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abstract = "In the isolated rat kidney perfused with Tyrode's solution and prelabeled with [3H]norepinephrine, we examined the effect of angiotensin (A)II, AI and synthetic tetradecapeptide (TDP) renin substrate on overflow of tritium in the absence and presence of the inhibitors of the renin-A system to assess the possible modulation by locally generated A of release of the adrenergic transmitter. Infusion of AII (0.3-10 ng/ml), AI (3-30 ng/ml) or synthetic TDP renin substrate (10-100 ng/ml) into the kidney increased perfusion pressure and enhanced the output of tritium and associated rise in perfusion pressure elicited by renal nerve stimulation. The increase in stimulation-induced output of tritium produced by these agents consisted primarily of intact [3H]norepinephrine. AI-converting enzyme inhibitors, SQ 20881 (2 μg/ml) or the diacid form of MK-421 (10 ng/ml), abolished the effect of AI but not that of AII or TDP renin substrate to produce vasoconstriction and to enhance the vascular response and tritium overflow caused by nerve stimulation. The AII competitive antagonist [Sarcosine1-Ala8]AII (1 μg/ml) abolished the facilitatory effects of AII, AI and TDP at the renal vascular adrenergic neuroeffector junction. The effect of a structurally dissimilar peptide, bradykinin, to enhance stimulation-induced renal vasoconstriction and tritium overflow was not altered by [Sarcosine1-Ala8]AII. These data indicate that the facilitatory effect of AI at the renal vascular adrenergic neuroeffector junction is due to its conversion to AII, whereas the effect of TDP renin substrate is due either to its direct conversion to AII or to a direct action on AII receptors at the adrenergic neuroeffector-junction. We conclude that AII generated locally in the kidney may contribute to the regulation of vascular tone by influencing the activity of adrenergic nervous system.",
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AU - Boke, T.

AU - Malik, Kafait

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N2 - In the isolated rat kidney perfused with Tyrode's solution and prelabeled with [3H]norepinephrine, we examined the effect of angiotensin (A)II, AI and synthetic tetradecapeptide (TDP) renin substrate on overflow of tritium in the absence and presence of the inhibitors of the renin-A system to assess the possible modulation by locally generated A of release of the adrenergic transmitter. Infusion of AII (0.3-10 ng/ml), AI (3-30 ng/ml) or synthetic TDP renin substrate (10-100 ng/ml) into the kidney increased perfusion pressure and enhanced the output of tritium and associated rise in perfusion pressure elicited by renal nerve stimulation. The increase in stimulation-induced output of tritium produced by these agents consisted primarily of intact [3H]norepinephrine. AI-converting enzyme inhibitors, SQ 20881 (2 μg/ml) or the diacid form of MK-421 (10 ng/ml), abolished the effect of AI but not that of AII or TDP renin substrate to produce vasoconstriction and to enhance the vascular response and tritium overflow caused by nerve stimulation. The AII competitive antagonist [Sarcosine1-Ala8]AII (1 μg/ml) abolished the facilitatory effects of AII, AI and TDP at the renal vascular adrenergic neuroeffector junction. The effect of a structurally dissimilar peptide, bradykinin, to enhance stimulation-induced renal vasoconstriction and tritium overflow was not altered by [Sarcosine1-Ala8]AII. These data indicate that the facilitatory effect of AI at the renal vascular adrenergic neuroeffector junction is due to its conversion to AII, whereas the effect of TDP renin substrate is due either to its direct conversion to AII or to a direct action on AII receptors at the adrenergic neuroeffector-junction. We conclude that AII generated locally in the kidney may contribute to the regulation of vascular tone by influencing the activity of adrenergic nervous system.

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M3 - Article

VL - 226

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EP - 907

JO - Journal of Pharmacology and Experimental Therapeutics

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SN - 0022-3565

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