Distinct vascular actions of epidermal growth factor-urogastrone and transforming growth factor-alpha.
We compared the effects of epidermal growth factor-urogastrone (EGF-URO) with those of transforming growth factor-alpha (TGF-alpha) on regional blood flow in the anesthetized dog in vivo, and on isolated canine helical coronary artery strips in vitro. Like EGF-URO, TGF-alpha was a potent stimulator of femoral arterial blood flow in vivo; and, when added to the tissue bath in vitro before an agonist, TGF-alpha like EGF-URO was a potent inhibitor of the contractile responses of helical coronary arterial strips to various smooth muscle agonists: norepinephrine (NE), prostaglandin F2 alpha (PGF alpha) and potassium chloride (KCl). Nonetheless, there were marked differences between EGF-URO and TGF-alpha in terms of the two biological responses measured. In terms of blood flow, although the ED50 for the increase in blood flow was similar for EGF-URO and TGF-alpha (ED50 = 0.4 micrograms EGF-URO equivalents per dose), the maximum responsiveness to TGF-alpha (130% increase in flow) was substantially greater than the maximum response to EGF-URO (70% increase in flow). Furthermore, TGF-alpha did not cause tachyphylaxis to subsequent doses of TGF-alpha, whereas a prior dose of either EGF-URO or TGF-alpha desensitized markedly the blood flow preparations to EGF-URO. Different desensitization patterns for the actions of EGF-URO and TGF-alpha also were observed in the arterial strip preparations. The inhibitory action of EGF-URO for agonist (NE, PGF2 alpha or KCl)-mediated contraction was diminished with repeated exposure of the tissue to EGF-URO, whereas the inhibitory action of TGF-alpha persisted with repetitive tissue exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology; D015237:Dinoprost; D004285:Dogs; D004361:Drug Tolerance; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015291:Transforming Growth Factors
D010455:Peptides; D011460:Prostaglandins F; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D015237:Dinoprost; D000109:Acetylcholine; D002118:Calcium