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On the pharmacology of venous smooth muscle from dog and man
Abstract:
Changes in tension of spiral strips from canine and human veins induced by various drugs are compared with results from the literature on human veins. The order of potencies of alpha-adrenoceptor stimulating amines (adrenaline greater than noradrenaline greater than dopamine greater than isoprenaline) is similar in human and canine veins. Comparison of the affinities for alpha-adrenoceptors of pharmacologic drugs (thymoxamine, indoramine, clonidine, dihydroergotamine) suggest marked differences between the alpha-adrenoceptors in veins from man and dog. Venoconstriction mediating 5-HT receptors and a very small population of beta-adrenoceptors exist in both species. Human veins are always dilated by histamine, while canine femoral veins in vitro are relaxed by lower and contracted by higher histamine concentrations. Prostaglandin F2 alpha constricts both canine femoral and human hand veins. PGA2 and PGE2 increase the tension of canine and human veins in vitro but dilate human hand veins in situ. The order of potencies of ergot alkaloids in canine femoral veins is ergotamine greater than dihydroergovaline greater than dihydroergotamine = dihydroergostine greater than methysergide, whereas in human hand veins it is ergotamine = dihydroergovaline greater than methysergide greater than dihydroergotamine greater than dihydroergostine. In dogs the venoconstrictor effect of ergotamine is mediated by at least 3 mechanisms: stimulation of [1] alpha-adrenoceptors, [2] 5-HT receptors and [3] endogenous prostaglandin synthesis. Stimulation of alpha-adrenoceptors by dihydroergotamine and of 5-HT receptors by ergotamine was confirmed on human hand veins in situ. Prejunctional receptors at sympathetic nerve terminals are involved in the regulation of venous tone. Inhibitory alpha-adrenoceptors, dopamine and PGE2 receptors as well as facilitating beta-adrenoceptor existing at human vasoconstrictor nerves may be stimulated or blocked by pharmacologic drugs thereby modifying venous tone.