Differential activation of adrenoceptor subtypes by noradrenaline applied from the intimal or adventitial surfaces of rat isolated tail artery.
1. The vasoconstrictor effects of noradrenaline applied to the intimal and adventitial surfaces of perfused segments of rat tail artery in the presence and absence of endothelium were studied. 2. Noradrenaline was about six times more potent as a vasoconstrictor when applied to the intimal than to the adventitial surface. Cocaine (25 mumol/L) enhanced responses to adventitial noradrenaline to a greater extent than those to intimal noradrenaline. A high concentration of propranolol (1 mumol/L) had a similar effect. 3. The vasoconstriction elicited by adventitial noradrenaline declined from a peak whereas that to intimal noradrenaline remained steady. A low concentration of propranolol (0.1 mumol/L) abolished the decline in the response to adventitial noradrenaline. 4. The alpha 1- and alpha 2-adrenoceptor antagonists prazosin (1 nmol/L) and idazoxan (100 nmol/L) significantly reduced responses to intimal and adventitial noradrenaline in the presence or absence of endothelium. 5. Removal of endothelium enhanced responses to intimal but not adventitial noradrenaline. Idazoxan produced a significantly greater reduction of responses to noradrenaline in the absence than in the presence of endothelium, and was more effective against intimal than adventitial noradrenaline. Similar effects were produced by the nitric oxide synthase inhibitor L-NAME (30 mumol/L). 6. It was concluded that noradrenaline acts on both alpha 1- and alpha 2-adrenoceptors to produce vasoconstriction: the alpha 1-adrenoceptors appear to be uniformly distributed, whereas alpha 2-adrenoceptors are located nearer the intima. Intimal noradrenaline also acts on endothelial alpha 2-adrenoceptors to release EDRF which counteracts the vasoconstrictor action of noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
Rajanayagam
M A
MA
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Rand
M J
MJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000648:ultrastructure; D003042:Cocaine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D013623:Tail / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D009569:Nitric Oxide; D001120:Arginine; D011433:Propranolol; D003042:Cocaine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine