Role of prejunctional beta adrenoceptors in rat cardiac sympathetic neurotransmission.
This study examines the role of prejunctional beta adrenoceptors in the modulation of sympathetic neurotransmission in the rat heart. Under anesthesia, the heart with right cardiac sympathetic nerves attached was isolated and perfused with Krebs' bicarbonate buffer containing cocaine (10 microM), corticosterone (40 microM) and atropine (6 microM). Stimulation of sympathetic nerves at frequencies of 0.05 to 3 Hz (15 pulses, supramaximal voltage, 2-msec pulse duration) produced a pronounced frequency-dependent increase in heart rate. A maximal increase of 89 +/- 10 bpm was obtained at 3 Hz. Propranolol (0.1 microM) had no significant effect on the stimulus-induced NE overflow in the absence and presence of alpha adrenoceptor blockade alone or combined with adenosine receptor blockade. The beta-2 adrenoceptor agonist salbutamol increased stimulus-induced NE overflow (15 pulses) at 0.1 Hz but not at 0.5 Hz. Alpha adrenoceptor blockade did not alter the salbutamol-evoked facilitation at 0.1 Hz but revealed salbutamol-evoked facilitation at 0.5 Hz. Salbutamol did not alter NE overflow at 1 Hz even in the presence of alpha adrenoceptor blockade. In conclusion, prejunctional beta adrenoceptor facilitation of NE overflow is frequency and alpha adrenoceptor modulated. At low frequency (0.1 Hz), beta adrenoceptor-mediated facilitation is maximal and alpha adrenoceptor independent; at intermediate frequency (0.5 Hz) it is alpha adrenoceptor restrained and it is absent at 1 Hz. Finally, NE does not modulate its own release via the prejunctional beta adrenoceptors.
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, TX 77204-5515.
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Apparsundaram
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Eikenburg
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D009435:Synaptic Transmission
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000420:Albuterol; D009638:Norepinephrine