Prolonged treatment with (+/-) propranolol induces supersensitivity to (L)noradrenaline in mesenteric arteries in the rat.
In the isolated perfused mesenteric arteries of the rat, neither (+/-) propranolol (0.1 microM) nor (+/-)isoproterenol (0.05 microM) modified the overflow of DL-[3H]noradrenaline (DL-[3H]NA) induced by sympathetic nerve stimulation at either 5 or 10 Hz. The blockade of alpha presynaptic receptors with phentolamine (4.7 microM) increased the 3H-transmitter overflow at 5 and 10 Hz. (+/-)Propranolol (0.1 microM) failed to modify this effect. Vasoconstrictor responses to exogenous NA or sympathetic nerve stimulation were not modified by (+/-)propranolol (0.1 microM). Prolonged treatment with (+/-)propranolol (7 mg/kg) for 15 days potentiates responses to both exogenous NA and sympathetic nerve stimulation; however, the fractional release per pulse of DL-[3H]NA was not modified at either 5 or 10 Hz. These results provide no evidence to support the hypothesis that the release of NA is regulated by presynaptic beta-adrenoreceptors in the mesenteric arteries of the rat. The enhancement of vascular responses after prolonged treatment with propranolol could be caused by postsynaptic supersensitivity.
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000502:physiology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D007545:Isoproterenol; D009638:Norepinephrine; D010646:Phentolamine