Enhanced responsiveness of smooth muscle, impaired endothelium-dependent relaxation and the genesis of coronary spasm.
Pathophysiology and genesis of coronary artery spasm were examined in vivo and in vitro in Göttingen miniature pigs. Five of 36 consecutive pigs before endothelial denudation showed evidence of regional hyperconstriction after intracoronary administration of histamine (group 1). Histologic examination revealed intimal thickening along the spastic site. Because 5 pigs died during endothelial denudation, cholesterol feeding was randomly assigned to 13 of the remaining 26 pigs (group 2) and others were fed a regular low cholesterol diet (group 3) for 3 months. Regional coronary hyperconstriction was also evident after intracoronary administration of histamine at the site of denudation, and the degree of constriction was 78 +/- 3 and 74 +/- 4% in groups 2 and 3, respectively. Because the intimal thickening was confirmed at the site of spasm in groups 2 and 3, spontaneous as well as denudation-induced intimal thickening accompanied the enhanced responsiveness to histamine, irrespective of the level of serum cholesterol. However, the role of geometry on histamine-induced luminal narrowing was only 6% and was not physiologically significant. Augmented responses of the coronary artery to histamine, but not to phenylephrine or potassium chloride were reproduced in the nonbeating isolated heart preparations perfused at 90 mm Hg with oxygenated Krebs-Henseleit solution, and the degree and location of in vitro hyperconstriction were similar to that in vivo and were not attenuated after pretreatment with the nerve transmitter blockers, guanethidine (3 X 10(-6) M), atropine (10(-6) M) and tetrodotoxin (3 X 10(-7) M). Accordingly, spasm can be provoked without the influence of blood constituents and neural factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Tomoike
H
H
Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Egashira
K
K
Yamamoto
Y
Y
Nakamura
M
M
D000818:Animals; D003329:Coronary Vasospasm / Q000209:etiology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006632:Histamine / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000150:complications; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D013552:Swine; D014664:Vasodilation
D006632:Histamine