Interactions between circulating peptides and the central nervous system in hemodynamic regulation.
Enkephalins and endothelins are endogenous peptides, which, at least at pharmacologic doses, produce complex hemodynamic responses after intravenous administration. The enkephalins, when injected into conscious animal models and humans, increase blood pressure, heart rate and minute ventilation. This response occurs by activation of specific opiate receptors located outside the bloodbrain barrier; the actual mechanism involves an increase in adrenergic autonomic nervous system tone and a decrease in cholinergic tone. These opiate receptors may activate afferent fibers, perhaps nicotinic cholinoceptors; in many ways their properties are suggestive of chemoreceptors. Furthermore, enkephalin responses appear to be modulated by gamma-aminobutyric acid complexes, in that the reversal of the excitatory hemodynamic responses seen in the conscious state to vasodepressor responses after barbiturate anesthesia may result from alteration of the state of activation of the gamma-aminobutyric acid complex. The enkephalin receptors are localized to the vertebral artery vascular distribution; the specific site may be the area postrema, a blood-brain barrier-deficient circum-ventricular organ demonstrated to modulate heart rate and blood pressure and to represent a target site for circulating angiotensin II. Endothelin increases heart rate and blood pressure when infused slowly into conscious or anesthetized dogs, although barbiturates do blunt the increase in heart rate. The mechanism appears to involve modification of autonomic tone, but also some element of direct vasoconstrictor activity. Interestingly, rapid bolus doses of endothelin produce only vasodepressor responses, suggesting that the rate and concentration at which circulating endothelin reaches afferent receptors or vasoconstrictor sites on vascular smooth muscle may determine the net hemodynamic response observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Sander
G E
GE
Department of Medicine, Veterans Administration Medical Center, New Orleans, Louisiana.
Lowe
R F
RF
Given
M B
MB
Giles
T D
TD
D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000502:physiology*; D002552:Cerebral Ventricles / Q000378:metabolism / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology; D004285:Dogs; D016232:Endothelins; D004745:Enkephalins / Q000494:pharmacology / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000502:physiology*; D011957:Receptors, Opioid / Q000378:metabolism; D014711:Vertebral Artery / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D016232:Endothelins; D004745:Enkephalins; D010455:Peptides; D011957:Receptors, Opioid; D005680:gamma-Aminobutyric Acid