Blockade of noradrenaline‐induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea‐pig ears

Abstract

1. The study has examined the receptors mediating constriction produced by brief local application of noradrenaline (NA) to cutaneous arteries and arterioles in the ear vasculature of anaesthetized guinea-pigs. The innervation of the corresponding vascular segments has been examined immunohistochemically at the conclusion of the pharmacological experiments. 2. Small arteries of branch order 4 (4 degrees, 40-110 microns internal diameter) were more sensitive to the vasoconstrictor action of NA than were more proximal arteries of branch order 3 (3 degrees, 60-150 microns internal diameter), or more distal arteries and arterioles of branch orders 5 to 7 (5 degrees-7 degrees, 18-85 microns internal diameter). This higher sensitivity of 4 degrees arteries was maintained after blockade of neuronal uptake with desipramine (1 microM), and after blockade of beta-adrenoceptors with propranolol (1 microM). 3. NA-induced vasoconstrictions of distal arterioles (5 degrees-7 degrees) were abolished or greatly reduced by yohimbine (1 microM). The blockade by yohimbine decreased progressively with increasing vessel diameter of proximal arteries, while the blockade by prazosin (1 microM) increased progressively in arteries > 40 microns diameter. 4. In 3 degrees and 4 degrees arteries, a substantial component (approximately 50%) of NA-induced vasoconstrictions remained after combined treatment with yohimbine and prazosin, in the presence or absence of desipramine. These constrictions were not further reduced by benextramine (1-10 microM), but were abolished by dihydroergotamine (1-10 microM). Constrictions induced by ATP (0.1-1 mM) were not affected by dihydroergotamine. 5. 5-Hydroxytryptamine (3-100 microM) had a variable effect on 3 degree and 4 degree arteries including: concentration dependent constrictions (n = 3); small constrictions at some concentrations, and dilatations or no change in diameter at other concentrations (n = 6); concentration-dependent dilatations only (n = 3). The 5-HT2 receptor antagonist, ketanserin (0.1-0.3 micro M), did not affect NA-induced constrictions.6. In 16 arterial segments ranging from 3 degree arteries to 60 arterioles, there was a significant correlation between the presence of neuropeptide Y-immunoreactive (NPY-IR) sympathetic axons and the degree of blockade of NA-induced constrictions by yohimbine, prazosin and dihydroergotamine.7. These results demonstrate marked differences in the postsynaptic adrenoceptors mediating vasoconstriction to a bolus of NA applied briefly to the adventitial surface of different segments of the cutaneous vasculature of the guinea-pig ear. Furthermore, the presence or absence of adrenoceptors sensitive to blockade by yohimbine or prazosin is related to the proportion of sympathetic axons innervating each vascular segment which contain NPY-IR.