Vascular smooth muscle relaxation induced by epidermal growth factor is endothelium-dependent.
Epidermal growth factor (EGF) is released from platelets during aggregation. Because we thought that EGF played a role in vascular tone, we investigated its vascular reactivity using isolated rat aortic strips with and without the endothelium. In the presence of endothelium, EGF relaxed vascular smooth muscle precontracted with 40 mM K+, 10(-5) M prostaglandin F2 alpha or 10(-6) M norepinephrine. The relaxation induced by EGF was more prominent on the prostaglandin F2 alpha- and norepinephrine-induced contractions than on the K(+)-induced contraction. Atropine (10(-5) M) and aspirin (10(-5) M) had no effect on the EGF-induced relaxation, but methylene blue (10(-5) M) partly abolished the relaxation evoked by EGF. These results suggest that EGF relaxes vascular smooth muscle in the presence of the endothelium. They also suggest that EGF has an effect on the endothelium to produce relaxing factor independent of cyclooxygenase; the releasing factor activates soluble guanylate cyclase, resulting in relaxation of vascular smooth muscle through the production of cyclic GMP.
Namiki
A
A
Third Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Akatsuka
N
N
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009569:Nitric Oxide; D004815:Epidermal Growth Factor; D001285:Atropine; D015237:Dinoprost; D001241:Aspirin; D011188:Potassium; D008751:Methylene Blue; D009638:Norepinephrine