Hyperthermia-induced vasoconstriction of the carotid artery and the role of potassium channels.
Clinical experience and experimental studies have shown that hyperthermia can cause cerebral ischaemia and brain damage. By in vitro experiments with heating, we previously were able to induce carotid artery constriction. The objective of the present study was to clarify the mechanism of this thermal response. Isometric tension was recorded in rabbit carotid artery specimens using organ baths during stepwise temperature elevation. The heating responses were investigated at basal tone, in precontracted vessels, after blocking of adrenergic responses and administration of potassium (K)-channel activators and inhibitors. Stepwise heating of carotid artery strips from 37 degrees C to 47 degrees C induced reproducible graded contraction. The hyperthermic responses were not due to adrenergic stimulation, which were reduced and resistant to neurogenic blockade by tetrodotoxin. Heating-induced contractions were potentiated by the K-channel inhibitors tetraethylammonium, BaCl2, charybdotoxin, and the Na+/K+ ATPase inhibitor ouabain. Levcromakalim (BRL), a K+-channel activator, reduced heating induced contractions. Heating of carotid artery preparations induced reversible graded vasoconstriction proportional to temperature. The heating-induced contractions were not mediated by an adrenergenic process, but rather were due to inhibition of K+ channels, which increases Ca2+ entry. In vivo, this reaction may lead to a disturbance of autoregulation of cerebral blood flow and ischemia with brain damage.
Mustafa
Seham
S
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat, Kuwait.
Thulesius
Olav
O