Abstract

The development of tachyphylaxis or desensitization in a tissue upon repeated application of an agonist is a well-established phenomenon. To investigate the possible basis of vascular homologous tachyphylaxis, vasomotor responses in isolated cerebral and peripheral blood vessels from the cat, dog and rabbit upon repeated application of several agonists were examined using in vitro tissue bath techniques. Tachyphylaxis to vasodilator responses developed to repeated application of vasoactive intestinal polypeptide (VIP) but not to beta adrenergic agonist, forskolin, 8-bromo-cyclic AMP, sodium nitroprusside or 8-bromo-cyclic GMP in feline cerebral arteries. The tachyphylaxis to VIP-induced responses varied among regions and was greatest in the internal carotid artery (ICA), followed by the middle cerebral artery and least in the basilar artery (BA). Cerebral arteries also developed significant tachyphylaxis to constriction induced by repeated applications of neuropeptide Y (NPY), alpha-1 adrenergic agonist, but not to alpha-2 adrenergic agonist, acetylcholine (ACh) or KCl. The tachyphylaxis to constrictions induced by repeated application of neuropeptide Y (NPY) also varied among regions, but was different from that induced by VIP; it was greatest in the BA, followed by the middle cerebral artery and least in the ICA. Similar results were obtained in arteries without endothelial cells. The density of regional innervation of NPY-immunoreactive fibers, which is densest in ICA and sparsest in BA, parallels that of VIP-immunoreactive fibers in these three regions. There is no positive correlation between density of catecholamine fluorescence fibers and degree of tachyphylaxis to noradrenaline-induced constriction in cat ICA, dog saphenous arteries and rabbit ear arteries either.(ABSTRACT TRUNCATED AT 250 WORDS)