Modulation by the endothelium of sympathetic vasoconstriction in an in vitro preparation of the rat tail artery.
1. The influence of the endothelium on transmural electrical stimulation was investigated in isolated and perfused segments of the rat tail artery. Noradrenaline release (NA, quantified by h.p.l.c.-electrochemical detection) and changes in perfusion pressure (PP, measured at constant flow rate) were simultaneously recorded in unstimulated and stimulated arterial segments, in the absence and in the presence of drugs. The ratio PP/NA release (mmHg pg-1) was taken as an index of the noradrenergic effectiveness. 2. Removal of the endothelium produced an increase in NA release and PP, in unstimulated and stimulated arteries. This can be taken as evidence of an endothelium-derived inhibitory factor (EDIF) acting at the prejunctional level, inhibiting NA release. Furthermore, in unstimulated arteries, the ratio PP/NA release decreased suggesting the existence of an endothelium-derived contracting factor (EDCF). 3. Perfusion of arteries with N omega-nitro-L-arginine methyl ester (L-NAME, 10 microM) or methylene blue (MeB, 0.5 microM) had no effect on PP or NA release in unstimulated arteries. In stimulated arteries, both drugs potentiated the increase in PP without changing NA release and therefore, led to an increase in noradrenergic effectiveness. After removal of the endothelium, neither L-NAME nor MeB affected the increases in PP and NA release following electrical stimulation. 4. Carbachol (1 microM) attenuated both NA release and the increase in PP during electrical stimulation, and increased the ratio PP/NA release. L-NAME and MeB did not modify the inhibitory effect of carbachol on NA release, or the facilitatory effect of carbachol on the noradrenergic effectiveness. 5. Angiotensin II (All, 0.1 MicroM) potentiated the increase in PP, without modifying NA release following electrical stimulation, and facilitated the vasoconstriction induced by perfusion of NA. In the absence of endothelium, All potentiated both the increase in PP and NA release in arteries stimulated electrically but had no effect on the vasoconstriction induced by perfusion of NA. This suggests an endothelium dependent activity of All in this preparation.6. These findings suggest that, in the rat tail artery, sympathetic vasoconstriction is modulated by three endothelial factors: (1) nitric oxide (NO), the release ot which seems NA-dependent; (2) EDCF,predominant in the unstimulated state, the release of which; can be stimulated by All; and (3) EDIF,unmasked by removal of the endothelial layer, the release of which can be stimulated by All.
Laboratoire de Pharmacologie cardio-vasculaire, Faculté des Sciences Pharmaceutiques et Biologiques, Nancy, France.
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Thorin
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Atkinson
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000502:physiology*; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D009569:Nitric Oxide; D002217:Carbachol; D001120:Arginine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine