Skip to main content
SpringerLink
Log in

Role of angiotensin and sodium intake in cardiac noradrenaline release

  • Original Articles
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The effects of exogenous and of endogenous angiotensin on noradrenaline overflow were investigated in saline perfused rat hearts with intact sympathetic nerves. The overflow of endogenous noradrenaline induced by electrical stimulation of the left stellate ganglion was determined in the coronary venous effluent by HPLC. The activity of the renin-angiotensin system was modulated by varying of the nutritional sodium load prior to the experiments. Endogenous angiotensin formation was blocked by angiotensin-converting enzyme inhibitors.

Following high sodium intake, both angiotensin II (100 nmol/l) and angiotensin I (1 µmol/l) caused a marked increase of the electrically evoked noradrenaline overflow. After inhibition of the angiotensin-converting enzyme using captopril (350 nmol/l) or ramiprilat (50 nmol/l), angiotensin I (1 µmol/l) did not enhance noradrenaline overflow. This indicates an active cardiac angiotensin conversion, since the sole administration of captopril and ramiprilat did not affect noradrenaline overflow in rats with high sodium intake. Following low sodium intake, neither angiotensin II (100 nmol/l) nor angiotensin I (1 µmol/l) significantly affected noradrenaline overflow. Both captopril and ramiprilat, however, significantly reduced noradrenaline overflow induced by electrical stimulation, suggesting a facilitory action of endogenous angiotensin under these conditions.

This concept was substantiated when evaluating the noradrenaline overflow during control stimulations. Following low sodium intake, stimulation evoked noradrenaline overflow was higher as compared to that after nutritional sodium load. The results are in keeping with a sodium-dependent intracardiac formation of angiotensin II which facilitates noradrenaline release from sympathetic nerve terminals. Following low sodium intake, cardiac angiotensin II formation is active, as indicated by the suppression of noradrenaline release by angiotensin-converting enzyme inhibitors and the ineffectiveness of exogenous application of angiotensin II. In contrast, suppression of endogenous angiotensin 11 formation in sodium loaded animals sensitizes the sympathetic nerves to exogenous angiotensin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Brunner HR, Chang P, Wallach R, Sealey JE, Laragh JH (1972) Angiotensin II vascular receptors: Their avidity in relationship to sodium balance, the autonomic nervous system, and hypertension. J Clin Invest 51:58–67

    Google Scholar 

  • Carrière S, Cardinal J, Le Grimellec C (1980) Influence of sodium intake on catecholamine release by angiotensin and renal nerve stimulation in dogs. Can J Physiol Pharmacol 58:1092–1101

    Google Scholar 

  • Dahl LK, Knudsen KD, Heine MA, Leitl GJ (1968) Effects of chronic excess salt ingestion. Modification of experimental hypertension in the rat by variations in the diet. Circ Res 12:11–18

    Google Scholar 

  • Davis JO, Freeman RH (1976) Mechanisms regulating renin release. Physiol Rev 56:1–56

    Google Scholar 

  • Ellis JL, Burnstock G (1989) Angiotensin neuromodulation of adrenergic and purinergic co-transmission in the guinea pig vas deferens. Br J Pharmacol 97:1157–1164

    Google Scholar 

  • Hughes J, Roth RH (1971) Evidence that angiotensin enhances transmitter release during sympathetic nerve stimulation. Br J Pharmacol 41:239–255

    Google Scholar 

  • Khairallah PA (1972) Action of angiotensin on adrenergic nerve endings: Inhibition of norepinephrine uptake. Fed Proc 31:1351–1357

    Google Scholar 

  • Lindmar R, Muscholl E (1964) Die Wirkung von Pharmaka auf die Elimination von Noradrenalin aus der Perfusionsflüssigkeit und die Noradrenalinaufnahme in das isolierte Herz. Naunyn-Schmiedeberg's Arch Pharmacol 247:469–492

    Google Scholar 

  • Lindpaintner K, Jin M, Wilhelm MJ, Suzuki F, Linz W, Schoelkens BA, Ganten D (1988) Intracardiac generation of angiotensin and its physiologic role. Circulation 77 [Suppl I]:18–23

    Google Scholar 

  • Lindpaintner K, Jin M, Niedermaier N, Wilhelm MJ, Ganten D (1990) Cardiac angiotensinogen and its local activation in the isolated perfused beating heart. Circ Res 67:564–573

    Google Scholar 

  • Majewski H, Hedler L, Schurr C, Starke K (1984) Modulation of noradrenaline release in the pithed rabbit: A role for angiotensin II. J ardiovasc Pharmacol 6:888–896

    Google Scholar 

  • Majewski H (1989) Angiotensin II and noradrenergic transmission in the pithed rat. J Cardiovasc Pharmacol 14:622–630

    Google Scholar 

  • Molderings GJ, Likungu J, Hentrich F, Göthert M (1988) Facilitatory presynaptic angiotensin receptors on the sympathetic nerves of the human saphenous vein and pulmonary artery. Potential involvement in β-adrenoceptor-mediated facilitation of noradrenaline release. Naunyn-Schmiedeberg's Arch Pharmacol 338:228–233

    Google Scholar 

  • Nussberger J, Juillerat L, Perret F, Waeber B, Bellet M, Brunner J, Ménard J (1989) Need for plasma angiotensin measurements to investigate converting-enzyme inhibition in humans. Am Heart J 117:717–722

    Google Scholar 

  • Peach MJ (1981) Molecular actions of angiotensin. Biochem Pharmacol 30:2745–2751

    Google Scholar 

  • Peach MJ, Bumpus FM, Khairallah PA (1969) Inhibition of norepinephrine uptake in hearts by angiotensin II and analogs. J Pharmacol Exp Ther 167:291–299

    Google Scholar 

  • Richardt G, Waas W, Kranzhofer R, Mayer E, Schömig A (1987) Adenosine inhibits exocytotic release of endogenous noradrenaline in rat heart: A protective mechanism in early myocardial ischemia. Circ Res 61:117–123

    Google Scholar 

  • Richardt G, Lumpp U, Haass M, Schömig A (1990) Propranolol inhibits nonexocytotic noradrenaline release in myocardial ischemia. Naunyn-Schmiedeberg's Arch Pharmacol 341:50–55

    Google Scholar 

  • Roth RH (1972) Action of angiotensin on adrenergic nerve endings: Enhancement of norepinephrine biosynthesis. Fed Proc 31:1358–1364

    Google Scholar 

  • Rump LC, Majewski H (1987) Beta adrenoceptor facilitation of norepinephrine release is not dependent on local angiotensin II formation in the rat isolated kidney. J Pharmacol Exp Ther 243:1107–1112

    Google Scholar 

  • Schomig A, Fischer S, Kurz Th, Richardt G, Schömig E (1987) Nonexocytotic release of endogenous noradrenaline in the ischemic and anoxic rat heart: Mechanism and metaboic requirements. Circ Res 60:194–205

    Google Scholar 

  • Schwieler JH, Kahan T, Nussberger J, Hjemdahl P (1991) Influence of the renin-angiotensin system on sympathetic neurotransmission in canine skeletal muscle in vivo. Naunyn-Schmiedeberg's Arch Pharmacol 343:166–172

    Google Scholar 

  • Smedes F, Kraak JC, Poppe H (1982) Simple and fast solvent extraction system for selective and quantitative isolation of adrenaline, noradrenaline and dopamine from plasma and urine. J Chromatogr 231:25–39

    Google Scholar 

  • Starke K, Werner U Schümann HJ (1969) Wirkung von Angiotensin auf Funktion und Noradrenalinabgabe isolierter Kaninchenherzen in Ruhe und bei Sympathicusreizung. Naunyn-Schmiedeberg's Arch Pharmacol 265:170–186

    Google Scholar 

  • Starke K (1970) Interactions of angiotensin and cocaine on output of noradrenaline from isolated rabbit hearts. Naunyn-Schmiedeberg's Arch Pharmacol 265:383–386

    Google Scholar 

  • Starke K (1971) Action of angiotensin on uptake release and metabolism of 14C-noradrenaline by isolated rabbit hearts. Eur J Pharmacol 14:112–123

    Google Scholar 

  • Story DF, Ziogas J (1987) Interaction of angiotensin with noradrenergic neuroeffector transmission. Trends Pharmacol Sci 8:269–271

    Google Scholar 

  • Swales JD (1979) Arterial wall or plasma renin in hypertension? Clin Sci 56:293–298

    Google Scholar 

  • Szabo B, Hedler L, Schurr C, Starke K (1990) Peripheral presynaptic facilitatory effect of angiotensin II on noradrenaline release in anesthetized rabbits. J Cardiovasc Pharmacol 15:968–975

    Google Scholar 

  • Thurston H, Laragh JH (1975) Prior receptor occupancy as a determinant of the pressor activity of infused angiotensin II in the rat. Circ Res 36:113–117

    Google Scholar 

  • Zimmermann BG (1978) Actions of angiotensin an adrenergic nerve endings. Fed Proc 37:199–202

    Google Scholar 

  • Zimmermann BG (1981) Adrenergic facilitation by angiotensin: Does it serve a physiological function? Clin Sci 60:343–348

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, University of Heidelberg, Bergheimer Strasse 58, W-6900, Heidelberg, Germany

    Gert Richardt, Eckart Mayer & Albert Schömig

Authors
  1. Gert Richardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eckart Mayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Albert Schömig
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 320 — Herzfunktion and ihre Regulation)

Send offprint requests to G. Richardt at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Richardt, G., Mayer, E. & Schömig, A. Role of angiotensin and sodium intake in cardiac noradrenaline release. Naunyn-Schmiedeberg's Arch Pharmacol 344, 297–301 (1991). https://doi.org/10.1007/BF00183003

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00183003

Key words

Search

Navigation