Summary
In pithed dogs pressor responses to phenylephrine were completely inhibited 1 h after phenoxybenzamine 20 mg/kg i.v., but those to norepinephrine were only partially inhibited. The pressor effects of norepinephrine in phenoxybenzamine-treated animals were inhibited by yohimbine, 2.0 mg/kg i.v., but not by prazosin, 0.5 mg/kg i.v. In animals treated with phenoxybenzamine, 20 mg/kg i.v., plus propranolol, 5.0 mg/ kg i.v., the partially restored pressor response to epinephrine, and the responses to norepinephrine, were completely inhibited by yohimbine, 2.0 mg/kg i.v., partially inhibited by corynanthine, 5.0 mg/kg i.v., but not affected by prazosin, 0.5 mg/kg i.v. In additional animals treated with phenoxybenzamine plus propranolol, yohimbine, 10, 50, 200 and 500 μg/kg i.v., caused dose-related inhibition of both the partially restored pressor response to epinephrine, and the pressor responses to norepinephrine. It is concluded that: 1) phenoxybenzamine completely blocks α1, but not α2 vascular receptors; 2) the pressor effect of norepinephrine in phenoxybenzamine-treated animals, and the partially restored pressor effect of epinephrine in phenoxybenzamine-propranolol-treated animals, are both mediated by α2 vascular receptors which are resistant to blockade by phenoxybenzamine.
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References
Borowski E, Starke K, Ehrl H, Endo T (1977) A comparison of preand postsynaptic effects of α-adrenolytic drugs in the pulmonary artery of the rabbit. Neuroscience 2:285–296
Cambridge D, Davey MJ, Massingham R (1977) Prazosin, a selective antagonist of post-synaptic α-adrenoceptors. Br J Pharmacol 59:514P-515P
Constantine JW, Gunnell D, Weeks RA (in press) α1 and α2 vascular adrenoceptors in the dog. Eur J Pharmacol
Davis WG (1971) The reversal of phenoxybenzamine-produced α-adrenoceptor blockade by the isomers of propranolol and INPEA. J Pharm Pharmacol 23:332–338
Drew GM, Whiting SB (1979) Evidence for two distinct types of postsynaptic α-adrenoceptor in vascular smooth muscle in vivo. Br J Pharmacol 67:207–215
Dubocovich ML, Langer SZ (1974) Negative feed-back regulation of noradrenaline release by nerve stimulation in the perfused cat's spleen: differences in potency of phenoxybenzamine in blocking the pre-and post-synaptic adrenergic receptors. J Physiol 237:505–519
Farah MB, Langer SZ (1974) Protection by phentolamine against the effects of phenoxybenzamine on transmitter release elicited by nerve stimulation in the perfused cat heart. Br J Pharmacol 52:549–557
Garrett J, Malafaya-Baptista A, Osswald W (1966) Effects of pronethalol on the cardiovascular actions of catecholamines during blockade by phenoxybenzamine. Br J Pharmacol 27:459–467
Guimarães S (1969) Reversal by pronethelol of dibenamine blockade: a study on the seminal vesicle of the guinea-pig. Br J Pharmacol 36:594–601
Gulati OD, Gokhale SD, Udwadia BP (1965) Antagonism of adrenergic blockade by pronethalol. Arch Int Pharmacodyn 156:389–397
Harvey SC, Nickerson M (1954) Reactions of dibenamine and some congeners with substances of biologic interest in the relation to the mechanism of adrenergic blockade. J Pharmacol Exp Ther 112:274–290
Hull LD, Eltherington LG, Horita A (1960) The antagonism of adrenergic blockade by dichlorisoproterenol (DCI). Experientia 16:368–369
Moreira MG, Osswald W (1965) Pronethalol-induced reversal of adrenergic vasodepression. Nature 208:1006–1007
Mujic M, Van Rossum JM (1965) Comparative pharmacodynamics of sympathomimetic imidazolines; studies on intestinal smooth muscle of the rabbit and the cardiovascular system of the cat. Arch Int Pharmacodyn 155:432–449
Olivares GJ, Smith NT, Aronow L (1967) Effect of propranolol on alpha-adrenergic blockade in the dog and isolated rabbit aortic strip. Br J Pharmacol 30:240–250
Osswald W (1960) Reversal of adrenergic vasodepression. Arch Int Pharmacodyn 126:346–358
Patil PN, Tye A, May C, Hetey S, Miyagi S (1968) Steric aspects of adrenergic drugs. XI. Interactions of dibenamine and beta adrenergic blockers. J Pharmacol Exp Ther 163:309–319
Powell CE, Slater IH (1958) Blocking of inhibitory adrenergic receptors by a dichloro analog of isoproterenol. J Pharmacol Exp Ther 122:480–488
Sanders J, Miller DD, Patil PN (1975) Alpha adrenergic and histaminergic effects of tolazoline-like imidazolines. J Pharmacol Exp Ther 195:362–371
Sharma PL (1966) Interaction of adrenergic alpha and beta-receptor blocking agents on the blood pressure response to adrenaline and noradrenaline. Quart J Exp Physiol 51:256–261
Smith RD, Nash CB (1969) Effects of the beta adrenergic blocking agents, propranolol, Kö 592, and MJ-1999 on phenoxybenzamine blockade of norepinephrine. Arch Int Pharmacodyn 181:208–217
Starke K, Langer SZ (1979) A note of terminology for presynaptic receptors. In: Langer SZ, Starke K, Dubocovich ML (eds) Presynaptic receptors, advances in the biosciences, Vol 18. Pergamon Press, Oxford, pp 1–3
Starke K, Montel H, Schümann HJ (1971) Influence of cocaine and phenoxybenzamine on noradrenaline uptake and release. Naunyn-Schmiedeberg's Arch Pharmacol 270:210–214
Starke K, Endo T, Taube HD (1975a) Relative pre-and postsynaptic potencies of α-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 291:55–78
Starke K, Borowski E, Endo T (1975b) Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur J Pharmacol 34:385–388
Story ME, Bentley GA (1974) The effects of drugs and treatments upon adrenaline re-reversal in the rabbit. Arch Int Pharmacodyn 212:5–23
Weitzell R, Tanaka T, Starke K (1979) Pre-and postsynaptic effects of yohimbine stereoisomers on noradrenergic transmission in the pulmonary artery of the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 308:127–136
Yamamura HI, Horita A (1968) Effect of propranolol on the blockade of alpha adrenergic receptors. J Pharmacol Exp Ther 164:82–89
Yamamura HI, Horita A (1969) A further study of the effect of propranolol on the blockade of alpha adrenergic receptors. Eur J Pharmacol 7:258–263
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Constantine, J.W., Lebel, W. Complete blockade by phenoxybenzamine of α1- but not of α2-vascular receptors in dogs and the effects of propranolol. Naunyn-Schmiedeberg's Arch. Pharmacol. 314, 149–156 (1980). https://doi.org/10.1007/BF00504531
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DOI: https://doi.org/10.1007/BF00504531