Experimental sympathetic activation causes endothelial injury in the rabbit thoracic aorta via beta 1-adrenoceptor activation.
Sympathetic activation appears to accelerate the development of atherosclerosis, an effect that may be inhibited by beta-receptor blockade. It is unclear, however, which mechanisms mediate this effect. In view of the significance attached to endothelial injury in the initial phases of atherogenesis, we decided to test whether sympathetic activation might lead to an increase in endothelial injury. Chloralose anesthesia was used to induce sympathetic activation and the presence of intracellular IgG as a criterion of endothelial cell injury. The beta 1-selective beta-blocker metoprolol was used to evaluate if the effect(s) of sympathetic activation might be mediated by beta 1-adrenoceptors. In normal rabbits, the frequency of injured endothelial cells in unbranched areas of the thoracic aorta was 0.23%, compared with 1.93% in circumostial areas. Chloralose anesthesia caused significant increases in blood pressure, heart rate, and plasma norepinephrine, that is, caused sympathetic activation, and led to an approximately fivefold increase in the number of injured cells both in unbranched and in circumostial areas. This increase was totally inhibited by metoprolol pretreatment, indicating that it was mediated by beta 1-receptors. These observations suggest one possible mechanism that may connect sympathetic activation with atherogenesis and explain why beta-blockade protects against atherosclerosis.
Pettersson
K
K
Cardiovascular Research Laboratories, AB Hässle, Mölndal, Sweden.
Bejne
B
B
Björk
H
H
Strawn
W B
WB
Bondjers
G
G
D000758:Anesthesia; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology*; D001161:Arteriosclerosis / Q000473:pathology* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002470:Cell Survival; D002698:Chloralose / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D006339:Heart Rate / Q000187:drug effects; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D007074:Immunoglobulin G; D011943:Receptors, Adrenergic, beta; D002698:Chloralose; D008790:Metoprolol; D009638:Norepinephrine