Aminergic Histofluorescence and Contractile Responses to Transmural Electrical Field Stimulation and Norepinephrine of Human Middle Cerebral Arteries Obtained Promptly After Death

• Published in: Circulation research 1989-08, Vol.65 (2), p.316-324
• Main Authors: Duckworth, John W, Wellman, George C, Walters, Carrie L, Bevan, John A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Catecholamines - metabolism; Cerebral Arteries - drug effects; Cerebral Arteries - metabolism; Cerebral Arteries - physiology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Dose-Response Relationship, Drug; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Humans; Microscopy, Fluorescence; Middle Aged; Norepinephrine - pharmacology; Postmortem Changes; Vasoconstriction - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.65.2.316

The responses of cerebral arteries to catecholamines and sympathetic nerve stimulation show wide variation between animal species. We examined the catecholaminergic histofluorescence and the contractile responses elicited by transmural electrical field stimulation and norepinephrine (NE) in proximal segments of human middle cerebral artery (MCA) obtained during autopsy. Twenty-four percent of the specimens were obtained within 2 hours and 76% within 4 hours of death. A moderately dense catecholaminergic histofluorescence was seen in all segments of human MCA using the glyoxylic acid technique, counterstained with pontamine sky blue. However, only seven of 35 (20%) MCA segments tested showed tetrodotoxin-blocked transmural electrical field stimulation contractions, and all of these were harvested within 4 hours of death. The responses were mostly seen in the most proximal MCA segments and, at 32 Hz, only achieved 6±1% of the maximal tissue contraction. NE caused two distinct responses in human MCA segments. At low concentrations, it acts via an α-like adrenoreceptor to cause contractions 20±3% of the maximal tissue response. The NE ED50s for the three successive segments were not different from each other; the value for the most-proximal segment was 7.9±0.2×10 M. At concentrations above 10 M, this catecholamine acts on low-affinity sites resistant to α-adrenergic antagonists causing contractions that at 10 M reach 52±5% of the maximal tissue response. Our results suggest that it is important when studying human blood vessels to harvest them as soon as possible after death, that the smooth muscle response to sympathetic activation is small, frequently absent, and that the postsynaptic sympathetic mechanism includes not only α-adrenoceptors but low-affinity sites as well. (Circulation Research 1989;65:316-324)