Adrenergic and cholinergic interaction in central ventilatory control.
The ventrolateral medulla, which functions as integrator of cardiorespiratory control, contains cholinergic and adrenergic neurons. Exogenously administered cholinergic and adrenergic agents affect both ventilation and circulation. It is not clear whether these agents act in an independent or coordinate manner. beta-Adrenergic and alpha 2-adrenergic agents stimulate and depress the cardiorespiratory system, respectively. beta-Adrenergic and alpha 2-adrenergic agents stimulate and depress the production of adenosine 3',5'-cyclic monophosphate (cAMP), respectively. Increased intracellular cAMP may facilitate the release of acetylcholine (ACh). This work seeks to answer the following questions: 1) Are the cardiorespiratory effects of adrenergic agents secondary to possible changes in ACh release? 2) Does cAMP production have an intermediate role? By means of ventriculocisternal perfusion in anesthetized (pentobarbital sodium, 30 mg/kg) spontaneously breathing dogs, isoproterenol (ISO) increased ventilation (VE) 75% (P less than 0.05); heart rate and cardiac output were also increased (P less than 0.05). Esmolol (a beta-antagonist) blocked both the cardiovascular and ventilatory effects of ISO. Atropine (a cholinergic antagonist) blocked the ventilatory effects of ISO, but the circulatory changes persisted. Forskolin (a direct activator of adenylate cyclase) increased VE 51% (P less than 0.05), and its effect was also blocked by atropine. Clonidine decreased VE 42% (P less than 0.05); heart rate and cardiac output were also decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Burton
M D
MD
Medical Services (Pulmonary-Critical Care-Unit), Massachusetts General Hospital, Boston.
Johnson
D C
DC
Kazemi
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004285:Dogs; D007545:Isoproterenol / Q000494:pharmacology; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects / Q000502:physiology; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D011412:Propanolamines; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D005576:Colforsin; D015016:Yohimbine; D001285:Atropine; D000242:Cyclic AMP; D007545:Isoproterenol; C036604:esmolol; D003000:Clonidine; D000109:Acetylcholine