Effect of endothelium removal on stimulatory and inhibitory modulation of rat aortic prostacyclin synthesis.
1. Removal of the endothelium (DE) enhanced the in vitro release of prostacyclin (PGI2) by rat aortae in response to adrenaline (Ad), noradrenaline (NA), thromboxane A2 analogue U46619, phorbol dibutyrate (PDBU) and sodium fluoride (NaF) when assessed at 3 h post DE. At 6 h post DE, there were no differences between the dose-response curves obtained from aortic rings with or without endothelium. 2. At 3 h post DE the antagonism of Ad- and NA-stimulated PGI2 synthesis by yohimbine and prazosin, and NA-stimulated PGI2 synthesis by nifedipine was markedly reduced in aortae without endothelium when compared with controls. These effects were reversed by protracted incubation of aortic tissue post DE (6 h and 9 h). 3. Acetylcholine, carbachol, substance P and nitroprusside were without effect on de novo or NA-stimulated PGI2 synthesis, whether or not the endothelium was present and irrespective of incubation time, post-DE. 4. These results indicate that: (a) PGI2 synthesis linked to excitatory receptors (alpha-adrenoceptors, thromboxane A2) and associated systems (G proteins, protein kinase C) in the smooth muscle component of the rat aorta is not influenced by endothelium-derived relaxing factor (EDRF); (b) the changes of response to stimulators and inhibitors of PGI2 synthesis may be due to an increased reactivity of the vessels caused by the trauma of DE; and (c) vasodilators (parasympathomimetics, substance P and nitroprusside) that do not act directly on excitatory receptors do not influence PGI2 synthesis.
Jeremy
J Y
JY
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, London.
Dandona
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D009599:Nitroprusside; D015016:Yohimbine; D013373:Substance P; D015240:Phorbol 12,13-Dibutyrate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002217:Carbachol; D012969:Sodium Fluoride; D011464:Epoprostenol; D009543:Nifedipine; D000109:Acetylcholine; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine