Cardiac sympathetic nerve stimulation triggers coronary t-PA release.

• OBJECTIVE: This study was undertaken to determine whether stimulation of sympathetic cardiac nerves induces release of the thrombolytic enzyme tissue-type plasminogen activator (t-PA) in the coronary vascular bed. METHODS AND RESULTS: Anesthetized pigs were studied in an open chest model. Bilateral vagotomy was performed, and sympathetic cardiac nerves were activated by electrical stimulation (1 and 8 Hz). To evaluate possible mediating effects of increased heart rate and enhanced local blood flow, tachycardia was induced by pacing and hyperemia by local infusion of sodium nitroprusside and clevedipine. Furthermore, to study the effects of alpha- and beta-adrenergic receptor stimulation, phenylephrine and isoprenaline were infused locally. In response to low- and high-frequency sympathetic stimulation, mean coronary net release of total t-PA increased approximately 6- and 25-fold, respectively. Active t-PA showed a similar response pattern. Neither tachycardia nor coronary hyperemia stimulated t-PA release. In contrast, beta-adrenergic stimulation by isoprenaline induced an approximately 6-fold increase in coronary t-PA release, whereas no significant change in release rates occurred in response to alpha-adrenergic stimulation by phenylephrine. CONCLUSIONS: Stimulation of cardiac sympathetic nerves induces a marked coronary release of t-PA, and part of this response may be mediated through stimulation of beta-adrenergic receptors.

Nyckelord

Adrenergic alpha-Agonists

pharmacology

Adrenergic beta-Agonists

pharmacology

Animals

Blood Pressure

drug effects

Calcium Channel Blockers

pharmacology

Coronary Circulation

drug effects

Coronary Vessels

drug effects

secretion

Electric Stimulation

Endothelium

Vascular

drug effects

secretion

Female

Heart

innervation

Heart Rate

drug effects

Hyperemia

physiopathology

Isoproterenol

pharmacology

Male

Nitric Oxide Donors

pharmacology

Nitroprusside

pharmacology

Phenylephrine

pharmacology

Pyridines

pharmacology

Swine

Sympathetic Nervous System

physiology

Tachycardia

physiopathology

Tissue Plasminogen Activator

secretion

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