Effects of presynaptic modulators on Ca²⁺-induced noradrenaline relase from cardiac sympathetic nerves

Summary

Isolated rabbit hearts were perfused with Ca²⁺-free solution containing 139.7 mM K⁺ and 12.3 mM Na⁺ (Tyrode solution modified by omission of CaCl₂ and substitution of NaCl by KCl). The noradrenaline in the perfusate was determined spectrofluorimetrically. Perfusion with this solution induced release of noradrenaline, and introduction of 1.8 mM CaCl₂ for 2 min after perfusion with the Ca²⁺-free solution evoked additional release.

• 1. Methacholine (10⁻⁴M) and oxymetazoline (3.8×10⁻⁷M) decreased, whereas angiotensin II (10⁻⁹M) increased, the noradrenaline release evoked by 1.8 mM CaCl₂.

• 2. The changes of CaCl₂-induced noradrenaline release caused by these drugs were abolished by the corresponding antagonists (atropine, 3.5×10⁻⁶M; phentolamine, 10⁻⁶M, and Sar¹, Ile⁸-angiotensin II, 10⁻⁹M, respectively). When given alone, phentolamine (10⁻⁶M) increased, whereas atropine (3.5×10⁻⁶M) and Sar¹, Ile⁸-angiotensin II (10⁻⁹M) did not significantly alter the noradrenaline release evoked by 1.8 mM CaCl₂.

• 3. The noradrenaline release induced by perfusion of the heart with the Ca²⁺-free solution containing a low Na⁺ and a high K⁺ concentration was not affected by any of the drugs.

These findings provide additional evidence for the suggestion that modulation of noradrenaline release induced by activation of presynaptic muscarine, α-adrenergic, and angiotensin receptors is mediated via changes in the availability of Ca²⁺ ions for stimulus-release coupling.